PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 22731788-1 2012 We have applied a theoretical methodology, previously developed to evaluate the association and kinetic reactivation constants of oximes, comparing theoretical data obtained for human acetylcholinesterase (HsAChE) with in vitro results from Mus musculus AChE (MmAChE) previously reported in the literature. Oximes 130-136 acetylcholinesterase (Cartwright blood group) Homo sapiens 184-204 22808117-0 2012 Energetics of Ortho-7 (oxime drug) translocation through the active-site gorge of tabun conjugated acetylcholinesterase. Oximes 23-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-119 22360668-6 2012 The review describes the evaluation of the potency of newly developed oximes (especially the oxime K203) or combinations of oximes to reactivate nerve agent-inhibited acetylcholinesterase and to counteract the acute toxicity of nerve agents in comparison with single commonly used oxime (obidoxime, trimedoxime or HI-6). Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 167-187 22360668-6 2012 The review describes the evaluation of the potency of newly developed oximes (especially the oxime K203) or combinations of oximes to reactivate nerve agent-inhibited acetylcholinesterase and to counteract the acute toxicity of nerve agents in comparison with single commonly used oxime (obidoxime, trimedoxime or HI-6). Oximes 124-130 acetylcholinesterase (Cartwright blood group) Homo sapiens 167-187 22360668-6 2012 The review describes the evaluation of the potency of newly developed oximes (especially the oxime K203) or combinations of oximes to reactivate nerve agent-inhibited acetylcholinesterase and to counteract the acute toxicity of nerve agents in comparison with single commonly used oxime (obidoxime, trimedoxime or HI-6). Oximes 70-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 167-187 22808117-1 2012 Oxime drugs translocate through the 20 A active-site gorge of acetylcholinesterase in order to liberate the enzyme from organophosphorus compounds" (such as tabun) conjugation. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 62-82 21983245-0 2011 Potential of two new oximes in reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by organophosphate compounds: an in vitro study. Oximes 21-27 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-68 21799476-6 2011 Standard treatment involves the administration of intravenous atropine and an oxime to counteract acetylcholinesterase inhibition at the synapse, but the usefulness of oximes is still debated. Oximes 78-83 acetylcholinesterase (Cartwright blood group) Homo sapiens 98-118 21723318-11 2011 This indicates that peripheral and central AChE activities are not necessarily correlated after the treatment of OP compounds and/or oximes, which should be taken into account in the diagnosis and management of OP-exposed humans. Oximes 133-139 acetylcholinesterase (Cartwright blood group) Homo sapiens 43-47 21983245-8 2011 However, both newly developed oximes achieved similar reactivations rates that pralidoxime for chlorpyrifos and diazinon-inhibited AChE. Oximes 30-36 acetylcholinesterase (Cartwright blood group) Homo sapiens 131-135 21983245-10 2011 We conclude that both newly developed oximes seem to be promising reactivators of OP-inhibited AChE. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 95-99 21983245-3 2011 In this study, we compared the in vitro reactivation potency of two new oximes (oxime 1: butane-2,3-dionethiosemicarbazone; oxime 2: 3-(phenylhydrazono) butan-2-one) against the inhibition on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities induced by chlorpyrifos, diazinon and malathion. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 192-212 21983245-3 2011 In this study, we compared the in vitro reactivation potency of two new oximes (oxime 1: butane-2,3-dionethiosemicarbazone; oxime 2: 3-(phenylhydrazono) butan-2-one) against the inhibition on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities induced by chlorpyrifos, diazinon and malathion. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 214-218 21730071-5 2011 Here, we characterize 10 human (h) AChE mutants that, when coupled with an oxime, give rise to catalytic reactivation and aging resistance of the soman conjugate. Oximes 75-80 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 21726608-1 2011 The standard treatment of intoxication with organophosphorus (OP) compounds includes the administration of oximes acting as acetylcholinesterase (AChE) reactivating antidotes. Oximes 107-113 acetylcholinesterase (Cartwright blood group) Homo sapiens 124-144 21726608-1 2011 The standard treatment of intoxication with organophosphorus (OP) compounds includes the administration of oximes acting as acetylcholinesterase (AChE) reactivating antidotes. Oximes 107-113 acetylcholinesterase (Cartwright blood group) Homo sapiens 146-150 21726608-7 2011 In vitro testing of the nanoparticulate oxime formulations in primary porcine brain capillary endothelial cells (pBCEC) demonstrated an up to two times higher reactivation of OP-inhibited AChE than the free oximes. Oximes 40-45 acetylcholinesterase (Cartwright blood group) Homo sapiens 188-192 21803135-2 2011 To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 76-96 21803135-2 2011 To achieve this goal, oximes are administered for reactivation of inhibited acetylcholinesterase (AChE). Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 98-102 21730071-0 2011 Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 15-35 21930118-1 2011 Treatment of poisoning by highly toxic organophosphorus compounds (OP) with atropine and an acetylcholinesterase (AChE) reactivator (oxime) is of limited effectiveness in case of different nerve agents and pesticides. Oximes 133-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 92-112 21930118-1 2011 Treatment of poisoning by highly toxic organophosphorus compounds (OP) with atropine and an acetylcholinesterase (AChE) reactivator (oxime) is of limited effectiveness in case of different nerve agents and pesticides. Oximes 133-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 114-118 21504785-0 2011 Peripheral site ligand conjugation to a non-quaternary oxime enhances reactivation of nerve agent-inhibited human acetylcholinesterase. Oximes 55-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 114-134 21504785-2 2011 Conversely, non-ionic oxime reactivators often suffer from a lack of reactivating potency due to a low affinity for the active site of AChE. Oximes 22-27 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 21328273-2 2011 Standard treatment involves administration of intravenous atropine and oxime to reactivate inhibited acetylcholinesterase. Oximes 71-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-121 21605992-2 2011 Oximes are used as potential reactivators of OP-inhibited AChE due to their alpha-effect nucleophilic reactivity. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 58-62 21493754-10 2011 Protein expression of ACHE nonsynonymous variant D134H (SNP6) is impaired: this variant shows compromised stability and altered rates of organophosphate inhibition and oxime-assisted reactivation. Oximes 168-173 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 21402092-2 2011 However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Oximes 20-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-121 21402092-2 2011 However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Oximes 20-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 123-127 21464125-4 2011 Reactivation capacities of novel oximes are rank ordered by their relative reactivation rate constants at 0.67 mm compared with 2-pyridinealdoxime methiodide for reactivation of four organophosphate (sarin, cyclosarin, VX, and paraoxon) conjugates of human acetylcholinesterase (hAChE). Oximes 33-39 acetylcholinesterase (Cartwright blood group) Homo sapiens 279-284 21464125-6 2011 The 10 best reactivating oximes, predominantly hydroxyimino acetamide derivatives (for hAChE) and imidazole-containing aldoximes (for hBChE) also exhibited reasonable activity in the reactivation of tabun conjugates. Oximes 25-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-92 20807085-1 2011 The standard treatment of poisoning by organophosphorus compounds (OP) includes the reversible muscarine receptor antagonist atropine and oximes for the reactivation of OP-inhibited acetylcholinesterase (AChE). Oximes 138-144 acetylcholinesterase (Cartwright blood group) Homo sapiens 204-208 20807085-4 2011 These constants can be used to calculate reactivation velocities and oxime concentrations necessary for the reactivation of a desired fraction of inhibited AChE. Oximes 69-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 156-160 20807085-7 2011 Hereby, it has to be taken into account that an increase of affinity to OP-inhibited AChE is generally accompanied by an increased affinity to native AChE and subsequent reduction in oxime tolerance. Oximes 183-188 acetylcholinesterase (Cartwright blood group) Homo sapiens 85-89 20807085-8 2011 Hence, future developments of more effective oximes should consider kinetic demands by attempting to achieve a certain level of reactivity and affinity, preferentially towards OP-inhibited AChE. Oximes 45-51 acetylcholinesterase (Cartwright blood group) Homo sapiens 189-193 21151975-4 2010 The standard treatment of OP poisoning includes a combination of a muscarinic antagonist and an AChE reactivator (oxime). Oximes 114-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 96-100 20971170-1 2011 Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. Oximes 94-100 acetylcholinesterase (Cartwright blood group) Homo sapiens 126-146 20971170-1 2011 Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. Oximes 94-100 acetylcholinesterase (Cartwright blood group) Homo sapiens 148-152 21673941-6 2011 In the case of methamidophos-inhibited AChE, the lower oxime concentration (10(-5) M) had higher reactivation ability than the 10(-4) M concentration. Oximes 55-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 39-43 21673941-7 2011 Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10(-3)-10(-7) M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10(-5) M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for "pseudocatalytic" bioscavengers with BChE. Oximes 363-369 acetylcholinesterase (Cartwright blood group) Homo sapiens 151-155 20888357-8 2010 Due to the high reactivity of MMB-4 a rapid reactivation of inhibited AChE can be anticipated at adequate oxime concentrations which are substantially higher compared to HI-6. Oximes 106-111 acetylcholinesterase (Cartwright blood group) Homo sapiens 70-74 20688148-3 2011 The oxime 3c exhibited 45% regeneration of inhibited hAChE, in comparison to 34% and 24% regeneration by 2-PAM and obidoxime, respectively, at a concentration of 10(-3) M within 10 min. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 53-58 20688148-6 2011 This method involving the in vitro reactivation of inhibited hAChE may be useful for the screening of new oximes as reactivators. Oximes 106-112 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-66 21112787-0 2011 Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase. Oximes 23-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 109-129 21673941-0 2011 In vitro ability of currently available oximes to reactivate organophosphate pesticide-inhibited human acetylcholinesterase and butyrylcholinesterase. Oximes 40-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 103-123 21151975-8 2010 In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes. Oximes 44-50 acetylcholinesterase (Cartwright blood group) Homo sapiens 98-102 21151975-8 2010 In general, the nanoparticulate transported oximes achieved a better reactivation of OP-inhibited AChE than free oximes. Oximes 113-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 98-102 19883634-8 2010 Also oxime therapy in organophosphorus poisoning apparently gives perplexing results: Oximes are usually able to reactivate diethylphosphorylated AChE, but the efficiency may be occasionally markedly smaller than expected from kinetic data. Oximes 5-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 146-150 20510679-12 2010 Finally, these data emphasize the need to develop oximes with a higher selective affinity towards OP-inhibited hAChE in order to minimize possible side effects. Oximes 50-56 acetylcholinesterase (Cartwright blood group) Homo sapiens 111-116 20105433-5 2010 However, human AChE inhibited by certain OP is rather resistant to oxime-induced reactivation. Oximes 67-72 acetylcholinesterase (Cartwright blood group) Homo sapiens 15-19 20433814-13 2010 To examine directly how these differences affect oxime-mediated reactivation of AChE after inhibition by OPs, human and guinea pig red blood cell ghosts were prepared and used as sources of AChE, and the relative capacity of several different oximes to reactivate each OP-inhibited AChE were determined. Oximes 49-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 20635332-6 2010 It seems obvious that oximes are weakly penetrating the BBB, with minimal brain AChE reactivation (<5%) in important functional areas, such as the ponto-medullar. Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 20412789-0 2010 Interaction kinetics of oximes with native, phosphylated and aged human acetylcholinesterase. Oximes 24-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-92 20412789-1 2010 Oximes are commonly used nucleophilic reactivators of alkyl phosphorylated and alkyl methylphosphonylated acetylcholinesterase (AChE) and butyrylcholinesterase. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-126 20412789-1 2010 Oximes are commonly used nucleophilic reactivators of alkyl phosphorylated and alkyl methylphosphonylated acetylcholinesterase (AChE) and butyrylcholinesterase. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 128-132 20412789-3 2010 In this study we determined kinetic constants for interaction of three triazole containing oximes with native human AChE, enzyme diethylphosphorylated by paraoxon, enzyme phosphonylated by VX and cyclosarin as well as enzyme aged upon phosphonylation by soman. Oximes 91-97 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-120 20412789-4 2010 Stopped-flow kinetics of oxime interaction was monitored using quenching of intrinsic tryptophan fluorescence of AChE as an indicator of oxime binding. Oximes 25-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-117 20412789-4 2010 Stopped-flow kinetics of oxime interaction was monitored using quenching of intrinsic tryptophan fluorescence of AChE as an indicator of oxime binding. Oximes 137-142 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-117 20417629-1 2010 Catalytic activity of acetylcholinesterase (AChE; EC 3.1.1.7) was studied in the presence of oximes HI-6, K114, K127 and K203, and inhibition constants were determined for the reversible enzyme-inhibitor complex (K(I)). Oximes 93-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-42 20417629-1 2010 Catalytic activity of acetylcholinesterase (AChE; EC 3.1.1.7) was studied in the presence of oximes HI-6, K114, K127 and K203, and inhibition constants were determined for the reversible enzyme-inhibitor complex (K(I)). Oximes 93-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 44-48 20417629-3 2010 Molecular modelling of AChE-oxime complexes was used to determine amino acid residues of the active site involved in the interactions. Oximes 28-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 23-27 20417629-6 2010 The weakest inhibitor, K127, also formed several hydrogen bonds with the active site residues, but due to its long linker it was more likely stabilized at the peripheral site (Tyr124), which could explain lower AChE affinity for this oxime. Oximes 234-239 acetylcholinesterase (Cartwright blood group) Homo sapiens 211-215 19883634-8 2010 Also oxime therapy in organophosphorus poisoning apparently gives perplexing results: Oximes are usually able to reactivate diethylphosphorylated AChE, but the efficiency may be occasionally markedly smaller than expected from kinetic data. Oximes 86-92 acetylcholinesterase (Cartwright blood group) Homo sapiens 146-150 19883634-9 2010 Dimethylphosphorylated AChE is in general less amenable to oxime therapy, which largely fails in some cases of dimethoate poisoning where aging was much faster than expected from a dimethylphosphorylated enzyme. Oximes 59-64 acetylcholinesterase (Cartwright blood group) Homo sapiens 23-27 19917271-2 2010 The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Oximes 68-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-46 19917271-2 2010 The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Oximes 68-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-52 19917271-2 2010 The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Oximes 68-73 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-46 19917271-2 2010 The presently established acetylcholinesterase (AChE) reactivators (oximes), e.g. obidoxime and pralidoxime, are insufficient against a number of nerve agents and there is ongoing debate on the benefit of oxime treatment in human OP pesticide poisoning. Oximes 68-73 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-52 19917271-5 2010 Kinetic studies on the various interactions between erythrocyte AChE from various species, structurally different OP and different oximes provided a basis for the initial assessment of the ability of oximes to reactivate inhibited AChE. Oximes 200-206 acetylcholinesterase (Cartwright blood group) Homo sapiens 64-68 19917271-5 2010 Kinetic studies on the various interactions between erythrocyte AChE from various species, structurally different OP and different oximes provided a basis for the initial assessment of the ability of oximes to reactivate inhibited AChE. Oximes 200-206 acetylcholinesterase (Cartwright blood group) Homo sapiens 231-235 19917271-6 2010 In the present study, in vitro enzyme-kinetic and pharmacokinetic data from a minipig model of dimethoate poisoning and oxime treatment were used to calculate dynamic changes of AChE activities. Oximes 120-125 acetylcholinesterase (Cartwright blood group) Homo sapiens 178-182 20600799-6 2010 Overall, the study reveals that the oxime 4P-2 may have therapeutic potential in the reactivation of human AChE inhibited by sarin. Oximes 36-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 107-111 20406208-2 2010 Human malathion poisoning has been treated with oximes (mainly pralidoxime) in an attempt to reactivate OP-inhibited acetylcholinesterase (AChE). Oximes 48-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 139-143 20542100-1 2010 OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Oximes 71-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-58 20542100-1 2010 OBJECTIVES: Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Oximes 71-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 60-64 20546883-5 2010 The location of groups on the pyridine ring also influences passive transport into the brain; the optimum position of the oxime group was found to be position four (para) and substitution of the oxime group on the pyridine ring by carbamoyl or amidoxime group markedly decreased penetration of AChE reactivators into the CNS. Oximes 122-127 acetylcholinesterase (Cartwright blood group) Homo sapiens 294-298 21152278-0 2010 Reactivation of human acetylcholinesterase and butyrylcholinesterase inhibited by leptophos-oxon with different oxime reactivators in vitro. Oximes 112-117 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-42 21152278-1 2010 We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Oximes 45-51 acetylcholinesterase (Cartwright blood group) Homo sapiens 84-104 21152278-1 2010 We have evaluated in vitro the potency of 23 oximes to reactivate human erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE) inhibited by racemic leptophos-oxon (O-[4-bromo-2,5-dichlorophenyl]-O-methyl phenyl-phosphonate), a toxic metabolite of the pesticide leptophos. Oximes 45-51 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-110 21152278-3 2010 In case of leptophos-oxon inhibited AChE, the best reactivation potency was achieved with methoxime, trimedoxime, obidoxime and oxime K027. Oximes 94-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 36-40 20192902-0 2010 Oxime K027: novel low-toxic candidate for the universal reactivator of nerve agent- and pesticide-inhibited acetylcholinesterase. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-128 21787634-0 2010 Reactivation of VX-inhibited AChE by novel oximes having two oxygen atoms in the linker. Oximes 43-49 acetylcholinesterase (Cartwright blood group) Homo sapiens 29-33 20202777-5 2010 Oxime-type compounds used as acetylcholinesterase (AChE, E.C.3.1.1.7) reactivators have been considered for the retention study. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 29-49 20202777-5 2010 Oxime-type compounds used as acetylcholinesterase (AChE, E.C.3.1.1.7) reactivators have been considered for the retention study. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 51-55 21787634-1 2010 Two newly developed AChE reactivators possessing two oxime groups in 4-position of the pyridinium rings with linkers CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) were tested for their potency to reactivate VX-inhibited AChE. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 20-24 20347021-3 2010 Reactivators (oximes) of inhibited AChE are a mainstay of treatment. Oximes 14-20 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 20929049-5 2010 Although new oximes that can reactivate both peripheral and cerebral AChE and other prophylactic agents such as human serum butyrylcholinesterase (Hu BChE), sodium bicarbonate, huperzine A (a reversible ChE inhibitor) with imidazenil (a GABAA receptor modulator) have been proved effective in animal models, systematic clinical trials in patients are warranted. Oximes 13-19 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-73 19737786-2 2009 This chemical structure affects their responsiveness to oxime-induced acetylcholinesterase (AChE) reactivation after poisoning. Oximes 56-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 92-96 20004171-6 2010 OP-inhibited butyrylcholinesterase and acetylcholinesterase can be reactivated with oximes provided the OP has not aged. Oximes 84-90 acetylcholinesterase (Cartwright blood group) Homo sapiens 39-59 20005727-2 2010 The purpose of the present study was to evaluate new oxime compounds to reactivate acetylcholinesterase (AChE) inhibited by the OP paraoxon. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 83-103 20005727-2 2010 The purpose of the present study was to evaluate new oxime compounds to reactivate acetylcholinesterase (AChE) inhibited by the OP paraoxon. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-109 20005727-7 2010 Interestingly, oximes with a heterocyclic linker inhibited AChE at higher concentration (10(-3)M), whereas their ability to reactivate was increased at lower concentrations (10(-4)M and 10(-5)M). Oximes 15-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 59-63 20028185-10 2010 The in silico pharmacophore model of oxime affinity for binding to GA-inhibited AChE was found to require a hydrogen bond acceptor, a hydrogen bond donor at the two terminal regions, and an aromatic ring in the central region of the oximes. Oximes 233-239 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 20028185-11 2010 The model was found to be well-correlated (R = 0.9) with experimental oxime affinity for binding to GA-inhibited AChE. Oximes 70-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-117 20028185-13 2010 These results provided the first predictive pharmacophore model of oxime affinity for binding toward GA-inhibited AChE. Oximes 67-72 acetylcholinesterase (Cartwright blood group) Homo sapiens 114-118 20402654-6 2010 Our results showed that oxime K048 reached promising reactivation activity in case of all tested AChE inhibitors, except cyclosarin, at oxime concentration 10(-3) M. At a concentration of 10(-5) M, which is more common for human use, only methylchlorpyrifos-inhibited AChE was reactivated. Oximes 24-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 97-101 20402654-6 2010 Our results showed that oxime K048 reached promising reactivation activity in case of all tested AChE inhibitors, except cyclosarin, at oxime concentration 10(-3) M. At a concentration of 10(-5) M, which is more common for human use, only methylchlorpyrifos-inhibited AChE was reactivated. Oximes 24-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 268-272 19642642-7 2009 Furthermore, the crystal structure of the ternary complex of the aged conjugate with 2-PAM revealed that the orientation of the oxime function does not permit nucleophilic attack on the phosphorus atom, thus providing a plausible explanation for its failure to reactivate the aged soman/AChE conjugate. Oximes 128-133 acetylcholinesterase (Cartwright blood group) Homo sapiens 287-291 20032868-0 2009 Novel bisquaternary oximes--reactivation of acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon. Oximes 20-26 acetylcholinesterase (Cartwright blood group) Homo sapiens 44-64 20156534-0 2010 Comparative study of oxime-induced reactivation of erythrocyte and muscle AChE from different animal species following inhibition by sarin or paraoxon. Oximes 21-26 acetylcholinesterase (Cartwright blood group) Homo sapiens 74-78 20156534-1 2010 Standard treatment of acute poisoning by organophosphorus compounds (OP) includes administration of an antimuscarinic (e.g. atropine) and of an oxime-based reactivator of OP-inhibited acetylcholinesterase (AChE). Oximes 144-149 acetylcholinesterase (Cartwright blood group) Homo sapiens 206-210 20156534-2 2010 A recently introduced dynamically working in vitro model with real-time determination of membrane-bound AChE activity was shown to be a very versatile and promising model to investigate oxime-induced reactivation kinetics of OP-inhibited enzyme. Oximes 186-191 acetylcholinesterase (Cartwright blood group) Homo sapiens 104-108 20156534-6 2010 In addition, the basic kinetic constants of inhibition, aging, spontaneous- and oxime-induced-reactivation of erythrocyte AChE from these species were determined with a standard static model. Oximes 80-85 acetylcholinesterase (Cartwright blood group) Homo sapiens 122-126 20028185-3 2010 Inhibited AChE can be reactivated by oximes, antidotes for OP exposure. Oximes 37-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 10-14 20028185-4 2010 However, OP intoxication caused by the nerve agent tabun (GA) is particularly resistant to oximes, which poorly reactivate GA-inhibited AChE. Oximes 91-97 acetylcholinesterase (Cartwright blood group) Homo sapiens 136-140 20028185-5 2010 In an attempt to develop a rational strategy for the discovery and design of novel reactivators with lower toxicity and increased efficacy in reactivating GA-inhibited AChE, we developed the first in silico pharmacophore model for binding affinity of GA-inhibited AChE from a set of 11 oximes. Oximes 286-292 acetylcholinesterase (Cartwright blood group) Homo sapiens 168-172 20028185-5 2010 In an attempt to develop a rational strategy for the discovery and design of novel reactivators with lower toxicity and increased efficacy in reactivating GA-inhibited AChE, we developed the first in silico pharmacophore model for binding affinity of GA-inhibited AChE from a set of 11 oximes. Oximes 286-292 acetylcholinesterase (Cartwright blood group) Homo sapiens 264-268 20028185-7 2010 Quantum chemical methods were sequentially used from semiempirical AM1 to hierarchical ab initio calculations to determine the stereoelectronic properties of nine oximes exhibiting affinity for binding to GA-inhibited AChE in vivo. Oximes 163-169 acetylcholinesterase (Cartwright blood group) Homo sapiens 218-222 20028185-10 2010 The in silico pharmacophore model of oxime affinity for binding to GA-inhibited AChE was found to require a hydrogen bond acceptor, a hydrogen bond donor at the two terminal regions, and an aromatic ring in the central region of the oximes. Oximes 37-42 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 20345348-4 2010 It also focuses on the organophosphorus nerve agents, their properties, effects and a large part describes various possibilities in treatments, mainly traditional oxime therapies based on reactivation of AChE. Oximes 163-168 acetylcholinesterase (Cartwright blood group) Homo sapiens 204-208 19761810-2 2009 Oximes, such as K027 and HLo-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-73 19761810-2 2009 Oximes, such as K027 and HLo-7, can reactivate tabun-inhibited human AChE (tabun-hAChE) whereas the activity of their close structural analogue HI-6 is notably low. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 81-86 19526299-2 2009 However, oximes themselves are also AChE inhibitors, albeit at higher concentrations, which is a major cause of their toxicity and may be a dose-limiting factor in oxime therapy. Oximes 9-15 acetylcholinesterase (Cartwright blood group) Homo sapiens 36-40 19465093-1 2009 Oximes, including 2-pyridinealdoxime methiodide (2-PAM), are reactivators of acetylcholinesterase (AChE) inhibited by organophosphate poisoning. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 77-97 19465093-1 2009 Oximes, including 2-pyridinealdoxime methiodide (2-PAM), are reactivators of acetylcholinesterase (AChE) inhibited by organophosphate poisoning. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-103 19586353-0 2009 In vitro oxime-assisted reactivation of paraoxon-inhibited human acetylcholinesterase and butyrylcholinesterase. Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 65-111 19586353-3 2009 METHODS: Eighteen structurally different oxime reactivators were tested for their in vitro ability to reactivate paraoxon-inhibited human erythrocyte acetylcholinesterase and human plasma butyrylcholinesterase to find out structure-activity relationship within this set of compounds. Oximes 41-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 150-170 19526299-2 2009 However, oximes themselves are also AChE inhibitors, albeit at higher concentrations, which is a major cause of their toxicity and may be a dose-limiting factor in oxime therapy. Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 36-40 19428926-1 2009 Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. Oximes 186-191 acetylcholinesterase (Cartwright blood group) Homo sapiens 122-126 19449818-4 2009 We have concluded that oximes reactivate AChE by a three-step mechanism in opposition to the four-step processes of the other modeled nucleophiles. Oximes 23-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-45 19449818-5 2009 In addition, our model suggests that oximes react with AChE in the deprotonated form (oximate). Oximes 37-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 55-59 19429253-1 2009 Previous kinetic studies investigating the interactions between human acetylcholinesterase (AChE), structurally different organophosphorus compounds (OP) and oximes did not reveal a conclusive structure-activity relationship of the different reactions. Oximes 158-164 acetylcholinesterase (Cartwright blood group) Homo sapiens 70-90 19428953-4 2009 For therapeutic monitoring of oxime treatment in OP poisoning, measurement of erythrocyte AChE is suitable because erythrocyte AChE is an easily accessible surrogate for synaptic AChE. Oximes 30-35 acetylcholinesterase (Cartwright blood group) Homo sapiens 90-94 19449818-1 2009 Oximes have been used as reactivators for organophosphorus-inhibited acetylcholinesterase (AChE). Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 91-95 19429253-7 2009 Pentylsarin-inhibited AChE could be reactivated by oximes, HI 6 being more potent than obidoxime. Oximes 51-57 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 19429253-9 2009 Unfortunately, no structure-activity relationship could be observed for the oxime-induced reactivation of inhibited AChE. Oximes 76-81 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-120 19428926-7 2009 Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE. Oximes 118-124 acetylcholinesterase (Cartwright blood group) Homo sapiens 147-151 18548743-2 2008 However, AChE inhibition by oximes themselves (as quantified by their intrinsic IC50) is the major cause of oxime toxicity and the dose-limiting factor. Oximes 28-34 acetylcholinesterase (Cartwright blood group) Homo sapiens 9-13 19150463-5 2009 This implies that the main beneficial effect of oximes may result from reactivation of AChE activity in respiratory muscles rather than in the brain. Oximes 48-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-91 19150463-7 2009 Albeit the concentration of oximes in the central nervous system is significantly lower than in the plasma, they do gain access into the brain and are able to reactivate inhibited local AChE. Oximes 28-34 acetylcholinesterase (Cartwright blood group) Homo sapiens 186-190 19150463-9 2009 In this review, we focus on the ability of oximes to act in the brain and protect the central nervous system from OP-induced injury, either by direct reactivation of AChE or by other pharmacological mechanisms. Oximes 43-49 acetylcholinesterase (Cartwright blood group) Homo sapiens 166-170 18548743-2 2008 However, AChE inhibition by oximes themselves (as quantified by their intrinsic IC50) is the major cause of oxime toxicity and the dose-limiting factor. Oximes 28-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 9-13 18547553-4 2008 These oximes inhibited AchE with inhibitory potency (IC(50)) ranging from 0.02 to 1.0 mM. Oximes 6-12 acetylcholinesterase (Cartwright blood group) Homo sapiens 23-27 18855728-9 2008 The potency of all newly synthesized oximes to reactivate tabun-inhibited AChE is comparable with obidoxime with the exception of K074 that is significantly more efficacious in the brain. Oximes 37-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 74-78 18501341-0 2008 Oximes: Reactivators of phosphorylated acetylcholinesterase and antidotes in therapy against tabun poisoning. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 39-59 18501341-1 2008 One of the therapeutic approaches to organophosphate poisoning is to reactivate AChE with site-directed nucleophiles such as oximes. Oximes 125-131 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 18501341-3 2008 We tested oximes varying in the type of ring (pyridinium and/or imidazolium), the length and type of the linker between rings, and in the position of the oxime group on the ring to find more effective oximes to reactivate tabun-inhibited human erythrocyte AChE. Oximes 201-207 acetylcholinesterase (Cartwright blood group) Homo sapiens 256-260 18501341-7 2008 Since the reactivating efficacy of the oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these oximes is indeed primarily related to the reactivation of tabun-phosphorylated AChE. Oximes 39-45 acetylcholinesterase (Cartwright blood group) Homo sapiens 232-236 18501341-7 2008 Since the reactivating efficacy of the oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these oximes is indeed primarily related to the reactivation of tabun-phosphorylated AChE. Oximes 153-159 acetylcholinesterase (Cartwright blood group) Homo sapiens 232-236 18547553-6 2008 The protective potency (P(50)) of all oximes in human erythrocyte AChE inhibited by soman and tabun could not be determined. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 66-70 18617161-3 2008 For the recovery of inhibited AChE, derivatives from the group of pyridinium or bispyridinium aldoximes (called oximes) are used. Oximes 97-103 acetylcholinesterase (Cartwright blood group) Homo sapiens 30-34 18617161-11 2008 From the data obtained, it is clear that only two from currently available oximes (obidoxime and trimedoxime) are good reactivators of paraoxon-inhibited AChE. Oximes 75-81 acetylcholinesterase (Cartwright blood group) Homo sapiens 154-158 18555982-2 2008 It has been demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited acetylcholinesterase (AChE). Oximes 49-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 146-150 18555982-3 2008 If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 67-71 18555982-6 2008 Results indicate that oxime reactivation of all three monkey AChEs was very similar to human AChE. Oximes 22-27 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-65 18565503-2 2008 The purpose of the present study was to evaluate new oxime antidotes to reactivate the inhibited AChE. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 97-101 18617161-0 2008 Potency of several oximes to reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by paraoxon in vitro. Oximes 19-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-66 18344198-1 2008 Oximes are enzyme reactivators used in treating poisoning with organophosphorus cholinesterase (AChE) inhibitors. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 96-100 18564794-3 2008 The morbidity and mortality with organophosphate poisoning is relatively high despite the use of atropine as specific antidotal therapy and oximes to reactivate acetylcholinesterase. Oximes 140-146 acetylcholinesterase (Cartwright blood group) Homo sapiens 161-181 18344198-2 2008 The oxime dose which can be safely administered is limited by the intrinsic toxicity of the substances such as their own AChE-inhibiting tendency. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 121-125 18220560-2 2007 The main drugs are anticholinergics that antagonize the effects of accumulated acetylcholine at the cholinergic synapses and cholinesterase reactivators (oximes) reactivating inhibited AChE. Oximes 154-160 acetylcholinesterase (Cartwright blood group) Homo sapiens 185-189 17977518-0 2008 Comparison of the oxime-induced reactivation of erythrocyte and muscle acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 71-91 17977518-1 2008 The purpose of these experiments was to compare oxime-induced reactivation rate constants of acetylcholinesterase from different human tissue sources inhibited by organophosphorus compounds. Oximes 48-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 93-113 18304715-1 2008 The efficacy of oxime treatment in soman poisoning is limited due to rapid aging of inhibited acetylcholinesterase (AChE). Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 94-114 18304715-1 2008 The efficacy of oxime treatment in soman poisoning is limited due to rapid aging of inhibited acetylcholinesterase (AChE). Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-120 18281016-0 2008 Effects of oximes on rate of decarbamylation of human red blood cell AChE measured with two different methods. Oximes 11-17 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-73 18281016-2 2008 The treatment options in soman poisoning are very limited due to rapid aging of the inhibited acetylcholinesterase (AChE), when the enzyme species is considered as irreversibly inhibited and resistant towards reactivation by oximes. Oximes 225-231 acetylcholinesterase (Cartwright blood group) Homo sapiens 94-114 18281016-2 2008 The treatment options in soman poisoning are very limited due to rapid aging of the inhibited acetylcholinesterase (AChE), when the enzyme species is considered as irreversibly inhibited and resistant towards reactivation by oximes. Oximes 225-231 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-120 18281016-6 2008 The question whether there is a possibility of an interaction between pre-treating carbamates and oximes at AChE arises. Oximes 98-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-112 18393843-10 2008 Oximes, by reactivating acetylcholinesterase, are important adjunct therapeutics in organophosphate poisoning. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 24-44 18220560-9 2007 An universality of oximes able to reactivate AChE inhibited by all OP is questioned and therefore, needs of development of new oximes is underlined. Oximes 19-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-49 17504181-3 2007 Oximes hydrolytically cleave the organophosphates from acetylcholinesterase (AChE), restoring enzymatic function. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 55-75 17382909-3 2007 Reactivators (oximes) of inhibited AChE are a mainstay of treatment. Oximes 14-20 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 17382909-4 2007 However, human AChE inhibited by certain OP, e.g. the phosphoramidates tabun and fenamiphos, is rather resistant towards reactivation by oximes while AChE inhibited by others, e.g. the phosphoramidate methamidophos is easily reactivated by oximes. Oximes 137-143 acetylcholinesterase (Cartwright blood group) Homo sapiens 15-19 17382909-4 2007 However, human AChE inhibited by certain OP, e.g. the phosphoramidates tabun and fenamiphos, is rather resistant towards reactivation by oximes while AChE inhibited by others, e.g. the phosphoramidate methamidophos is easily reactivated by oximes. Oximes 240-246 acetylcholinesterase (Cartwright blood group) Homo sapiens 15-19 17382909-6 2007 A clear structure-activity relationship of aging, spontaneous and oxime-induced reactivation kinetics could be determined with AChE inhibited by N-monoalkyl tabun analogues depending on the chain length of the N-alkyl residue. Oximes 66-71 acetylcholinesterase (Cartwright blood group) Homo sapiens 127-131 17370251-2 2007 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 83-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-61 17370251-2 2007 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 83-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 17370251-2 2007 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 83-88 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-61 17370251-2 2007 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 83-88 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 17370251-4 2007 The prospective oxime HI 6 is a weak reactivator of tabun- and pesticide-inhibited AChE, while the established oxime obidoxime mainly lacks efficacy with cyclosarin-inhibited enzyme. Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 83-87 17900152-1 2007 The reactivation of nerve agent-inhibited acetylcholinesterase (AChE) by oxime is the most important step in the treatment of nerve agent poisoning. Oximes 73-78 acetylcholinesterase (Cartwright blood group) Homo sapiens 64-68 17900152-4 2007 Several investigations have demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited AChE. Oximes 65-70 acetylcholinesterase (Cartwright blood group) Homo sapiens 140-144 17900152-5 2007 If the in vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely that the results of an in vivo animal study will reliably extrapolate to humans. Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 67-71 17900152-7 2007 Reactivation kinetic studies with five mono- and bis-pyridinium oximes showed that oxime reactivation of nerve agent-inhibited human AChE in most cases was faster than guinea pig AChE. Oximes 64-69 acetylcholinesterase (Cartwright blood group) Homo sapiens 133-137 17913691-2 2007 Therapeutic strategies are directed to antagonise overstimulation of muscarinic receptors with atropine and to reactivate inhibited AChE with oximes. Oximes 142-148 acetylcholinesterase (Cartwright blood group) Homo sapiens 132-136 17913691-11 2007 Oxime administration can be stopped when AChE is aged completely, but has to be continued as long as poison is present in the body and reactivation is possible. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-45 17443135-2 2007 Clinical treatment of nerve-agent poisoning is to use oxime-based antidotes to reactivate the inhibited AChE. Oximes 54-59 acetylcholinesterase (Cartwright blood group) Homo sapiens 104-108 17443135-4 2007 To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. Oximes 19-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 17443135-4 2007 To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. Oximes 99-105 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 17383875-4 2007 Notably, the oxime group in position four substantially increased the ability of the novel compounds to reactivate paraoxon-inhibited AChE. Oximes 13-18 acetylcholinesterase (Cartwright blood group) Homo sapiens 134-138 17504181-3 2007 Oximes hydrolytically cleave the organophosphates from acetylcholinesterase (AChE), restoring enzymatic function. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 77-81 17504181-9 2007 An universality of oximes able to reactivate AChE inhibited by all OP is questioned and trends (molecular modelling using neural network, structure-activity relationship, combination of reactivation and anticholinergic properties in one molecule) for future research are characterized. Oximes 19-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-49 17010492-10 2007 This oxime concentration reactivated RBC-AChE>20% of normal in most cases of OP poisoning by diethylphosphoryl compounds within a few hours. Oximes 5-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-45 16904807-2 2007 Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. Oximes 99-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 53-73 16904807-2 2007 Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. Oximes 99-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-79 16904807-5 2007 Since reactivation of OP-inhibited AChE is considered to be the main mechanism of action of oximes, human erythrocyte AChE can be exploited to test the efficacy of new oximes. Oximes 92-98 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 16904807-6 2007 Recently, a dynamic computer model was developed which allows the calculation of AChE activities at different scenarios by combining enzyme kinetics (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics. Oximes 210-215 acetylcholinesterase (Cartwright blood group) Homo sapiens 81-85 16904807-9 2007 The model presented may serve as a tool for evaluating the impact of carbamate pretreatment on oxime-induced reactivation of inhibited AChE, for defining effective oxime concentrations and for optimizing oxime treatment. Oximes 95-100 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 16904807-9 2007 The model presented may serve as a tool for evaluating the impact of carbamate pretreatment on oxime-induced reactivation of inhibited AChE, for defining effective oxime concentrations and for optimizing oxime treatment. Oximes 164-169 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 16904807-9 2007 The model presented may serve as a tool for evaluating the impact of carbamate pretreatment on oxime-induced reactivation of inhibited AChE, for defining effective oxime concentrations and for optimizing oxime treatment. Oximes 164-169 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 16904808-2 2007 Presently, standard treatment includes administration of an antimuscarinic agent (e.g. atropine) and a reactivator of inhibited AChE (oxime), but is considered to be rather ineffective with certain nerve agents due to low oxime effectiveness of the currently available oximes, obidoxime and pralidoxime. Oximes 134-139 acetylcholinesterase (Cartwright blood group) Homo sapiens 128-132 16904808-5 2007 A dynamic in vitro model, which allows the calculation of AChE activities at different scenarios was developed to facilitate the definition of effective oxime concentrations and the optimization of oxime treatment of OP poisoning of humans and may furthermore be helpful by designing animal experiments. Oximes 153-158 acetylcholinesterase (Cartwright blood group) Homo sapiens 58-62 16904808-5 2007 A dynamic in vitro model, which allows the calculation of AChE activities at different scenarios was developed to facilitate the definition of effective oxime concentrations and the optimization of oxime treatment of OP poisoning of humans and may furthermore be helpful by designing animal experiments. Oximes 198-203 acetylcholinesterase (Cartwright blood group) Homo sapiens 58-62 16904808-6 2007 The model is based on a combination of enzyme kinetics (inhibition, reactivation, aging) of AChE with OP, toxicokinetics and oxime pharmacokinetics. Oximes 125-130 acetylcholinesterase (Cartwright blood group) Homo sapiens 92-96 16904809-2 2007 OP inhibit acetylcholinesterase (AChE) and therefore standard treatment of respective poisoning includes AChE reactivators (oximes) in combination with antimuscarinic agents. Oximes 124-130 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-109 16904809-5 2007 Recently, we studied the reactivating potency of several oximes with human AChE inhibited by structurally different OP and observed remarkable differences depending on the OP and oxime. Oximes 57-63 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-79 16904809-5 2007 Recently, we studied the reactivating potency of several oximes with human AChE inhibited by structurally different OP and observed remarkable differences depending on the OP and oxime. Oximes 57-62 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-79 16904809-10 2007 In contrast, no structure-activity dependence could be observed for the oxime-induced reactivation of AChE and BChE inhibited by the compounds tested. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 102-106 16904809-11 2007 In general, OP-inhibited AChE and BChE were susceptible towards reactivation by oximes. Oximes 80-86 acetylcholinesterase (Cartwright blood group) Homo sapiens 25-29 16962227-4 2007 All oximes inhibited human AChE reversibly, and the inhibition potency increased in the following order Py-4-Br<Py-4-Cl<Py-4-CH(3)<Py-4-H<Py-4-NO(2). Oximes 4-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 27-31 16962227-5 2007 Although oximes Py-4-H and Py-4-NO(2) did not show significant reactivation ability, these oximes might be of interest as pre-treatment drugs due to their high affinity for the native AChE. Oximes 91-97 acetylcholinesterase (Cartwright blood group) Homo sapiens 184-188 16962227-7 2007 The orientations of all studied oximes in the active site of human AChE have been proposed by flexible ligand docking with AutoDock 3.0. Oximes 32-38 acetylcholinesterase (Cartwright blood group) Homo sapiens 67-71 17196318-2 2007 We discuss here how acetylcholinesterase (AChE), through appropriate mutations, becomes more susceptible to oxime reactivation. Oximes 108-113 acetylcholinesterase (Cartwright blood group) Homo sapiens 20-40 17196318-2 2007 We discuss here how acetylcholinesterase (AChE), through appropriate mutations, becomes more susceptible to oxime reactivation. Oximes 108-113 acetylcholinesterase (Cartwright blood group) Homo sapiens 42-46 17196318-4 2007 Accordingly, "Oxime-assisted Catalysis" by AChE provides a potential means for catalyzing the hydrolysis of organophosphates in plasma prior to their reaching the cellular target site. Oximes 14-19 acetylcholinesterase (Cartwright blood group) Homo sapiens 43-47 17265452-0 2007 In vitro oxime reactivation of red blood cell acetylcholinesterase inhibited by methyl-paraoxon. Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-66 17298091-0 2007 Oxime-induced reactivation of sarin-inhibited AChE: a theoretical mechanisms study. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-50 17298091-3 2007 The potential energy surface along the pathway of the reactivation reaction of sarin-inhibited AChE by oxime reveals that the reaction can occur quickly due to the relatively low energy barriers. Oximes 103-108 acetylcholinesterase (Cartwright blood group) Homo sapiens 95-99 17456837-6 2007 Oximes, as a part of antidotal therapy, ensure the recovery of phosphylated enzymes via a process denoted as reactivation of inhibited AChE. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 17456837-11 2007 An oxime HLo-7 seems to be an efficient reactivator of AChE inhibited by any of the four organophosphorus warfare agents. Oximes 3-8 acetylcholinesterase (Cartwright blood group) Homo sapiens 55-59 17456837-12 2007 According to the available literature, the oximes LuH-6 and TMB-4, although relatively toxic, are the most potent to induce reactivation of AChE inhibited by the majority of organophosphorus pesticides. Oximes 43-49 acetylcholinesterase (Cartwright blood group) Homo sapiens 140-144 17112559-3 2007 Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents, e.g. soman and cyclosarin. Oximes 14-20 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 17112559-5 2007 Reactivation of OP-inhibited AChE is considered to be the most important reaction of oximes. Oximes 85-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 29-33 17112559-6 2007 Clinical data from studies with pesticide-poisoned patients support the assumption that the various reactions between AChE, OP and oxime, i.e. inhibition, reactivation and aging, can be investigated in vitro with human AChE. Oximes 131-136 acetylcholinesterase (Cartwright blood group) Homo sapiens 219-223 18254274-0 2007 Evaluation of potency of known oximes (pralidoxime, trimedoxime, HI-6, methoxime, obidoxime) to in vitro reactivate acetylcholinesterase inhibited by pesticides (chlorpyrifos and methylchlorpyrifos) and nerve agent (Russian VX). Oximes 31-37 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-136 16982122-5 2006 In addition, since butyrylcholinesterase (BChE; EC 3.1.1.8) is considered an endogenous bioscavenger of anticholinesterase compounds and its interactions with oximes could be masked by AChE interactions, we evaluated kinetic parameters for interactions of tested oximes with native and tabun-inhibited human plasma BChE and compared them with results obtained previously for human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7). Oximes 159-165 acetylcholinesterase (Cartwright blood group) Homo sapiens 185-189 18072133-6 2006 However, oxime HI-6 (33%) and obidoxime (23%) seem to be the best AChE reactivators for human relevant doses (10(-4) M and lower). Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 66-70 17252938-1 2006 Antidotes currently used for organophosphorus pesticide and nerve agent intoxications consist of anticholinergics (atropine mainly) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivators called oximes. Oximes 196-202 acetylcholinesterase (Cartwright blood group) Homo sapiens 136-156 17252938-1 2006 Antidotes currently used for organophosphorus pesticide and nerve agent intoxications consist of anticholinergics (atropine mainly) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivators called oximes. Oximes 196-202 acetylcholinesterase (Cartwright blood group) Homo sapiens 158-162 16982122-5 2006 In addition, since butyrylcholinesterase (BChE; EC 3.1.1.8) is considered an endogenous bioscavenger of anticholinesterase compounds and its interactions with oximes could be masked by AChE interactions, we evaluated kinetic parameters for interactions of tested oximes with native and tabun-inhibited human plasma BChE and compared them with results obtained previously for human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7). Oximes 159-165 acetylcholinesterase (Cartwright blood group) Homo sapiens 415-419 16982122-8 2006 Therefore, BChE could scavenge tabun prior to AChE inhibition, but fast oxime-assisted reactivation of tabun-inhibited AChE or protection of AChE by oxime against inhibition with tabun would not be obstructed by interaction between BChE and oximes. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 119-123 16982122-8 2006 Therefore, BChE could scavenge tabun prior to AChE inhibition, but fast oxime-assisted reactivation of tabun-inhibited AChE or protection of AChE by oxime against inhibition with tabun would not be obstructed by interaction between BChE and oximes. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 119-123 16720069-2 2006 OP inhibit acetylcholinesterase (AChE), therefore, standard treatment includes AChE reactivators (oximes) in combination with antimuscarinic agents. Oximes 98-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 79-83 16971069-7 2006 All of these oximes showed esterase-like activity, and their strengths were consistent with those of known reactivators of inhibited AChE. Oximes 13-19 acetylcholinesterase (Cartwright blood group) Homo sapiens 133-137 17194020-8 2006 Moreover, from the obtained results it could be deduced that AChE reactivators with a functional oxime group in position-2 are the most potent AChE reactivators in the case of cyclosarin intoxications. Oximes 97-102 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-65 17194020-8 2006 Moreover, from the obtained results it could be deduced that AChE reactivators with a functional oxime group in position-2 are the most potent AChE reactivators in the case of cyclosarin intoxications. Oximes 97-102 acetylcholinesterase (Cartwright blood group) Homo sapiens 143-147 17194021-6 2006 Furthermore effects of two conventional oximes paralidoxime (A) and obidoxime (B) on reactivation of the inhibited hAChE were studied but low reactivity was shown by both the oximes. Oximes 40-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 115-120 16740352-2 2006 Presently, standard treatment of poisoning by OP includes administration of atropine as an antimuscarinic agent and of oximes, e.g. obidoxime or pralidoxime, as reactivators of OP-inhibited acetylcholinesterase (AChE), but is considered to be rather ineffective with certain nerve agents. Oximes 119-125 acetylcholinesterase (Cartwright blood group) Homo sapiens 212-216 16740352-4 2006 A computer simulation based on combination of AChE kinetic data (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics allows the calculation of AChE activities at different scenarios and may facilitate to define effective oxime concentrations and to optimize oxime dosage in OP poisoning. Oximes 125-130 acetylcholinesterase (Cartwright blood group) Homo sapiens 174-178 16740352-4 2006 A computer simulation based on combination of AChE kinetic data (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics allows the calculation of AChE activities at different scenarios and may facilitate to define effective oxime concentrations and to optimize oxime dosage in OP poisoning. Oximes 252-257 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-50 16740352-4 2006 A computer simulation based on combination of AChE kinetic data (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics allows the calculation of AChE activities at different scenarios and may facilitate to define effective oxime concentrations and to optimize oxime dosage in OP poisoning. Oximes 252-257 acetylcholinesterase (Cartwright blood group) Homo sapiens 174-178 16740352-4 2006 A computer simulation based on combination of AChE kinetic data (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics allows the calculation of AChE activities at different scenarios and may facilitate to define effective oxime concentrations and to optimize oxime dosage in OP poisoning. Oximes 252-257 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-50 16740352-4 2006 A computer simulation based on combination of AChE kinetic data (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics allows the calculation of AChE activities at different scenarios and may facilitate to define effective oxime concentrations and to optimize oxime dosage in OP poisoning. Oximes 252-257 acetylcholinesterase (Cartwright blood group) Homo sapiens 174-178 17288495-1 2006 The traditional therapeutic treatment of organophosphate cholinesterase inhibitor (nerve agents) poisoning consists of co-treatment with an antimuscarinic (atropine) and a reactivator of inhibited acetylcholinesterase (AChE), which contains a nucleophilic oxime function. Oximes 256-261 acetylcholinesterase (Cartwright blood group) Homo sapiens 197-217 17438836-6 2006 From obtained results, it can be deduced, that only reactivators with oxime group in position two are able to reactivate cyclosarin-inhibited AChE. Oximes 70-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 142-146 16193529-0 2006 Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: in vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxon. Oximes 5-11 acetylcholinesterase (Cartwright blood group) Homo sapiens 123-143 16623863-3 2006 Oximes counteract acetylcholine increase, resulting from AChE inhibition. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 57-61 16623863-6 2006 The usefulness of oxime in the reactivation process depends on its chemical structure and on the nerve agent whereby AChE is inhibited. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 117-121 16515465-5 2006 Anticholinergic drugs block effects of accumulated neurotransmitter acetylcholine at nicotinic and muscarinic receptor sites, while oximes reactivate AChE inhibited by OPCs. Oximes 132-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 150-154 16515465-7 2006 Therefore, to find new oximes able to sufficiently reactivate inhibited AChE (regardless of the type of OPCs) is still very important task for medicinal chemistry with the aim to improve the efficacy of antidotal treatment of the acute poisonings mentioned. Oximes 23-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-76 17438836-0 2006 Reactivation potency of new group of acetylcholinesterase reactivators and their comparison with currently available oximes. Oximes 117-123 acetylcholinesterase (Cartwright blood group) Homo sapiens 37-57 17288495-1 2006 The traditional therapeutic treatment of organophosphate cholinesterase inhibitor (nerve agents) poisoning consists of co-treatment with an antimuscarinic (atropine) and a reactivator of inhibited acetylcholinesterase (AChE), which contains a nucleophilic oxime function. Oximes 256-261 acetylcholinesterase (Cartwright blood group) Homo sapiens 219-223 17288500-13 2006 As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all the enzyme becomes aged. Oximes 37-42 acetylcholinesterase (Cartwright blood group) Homo sapiens 129-133 16293236-1 2005 Current antidotes for organophosphorus compounds (OP) poisoning consist of a combination of pretreatment with carbamates (pyridostigmine bromide), to protect acetylcholinesterase (AChE) from irreversible inhibition by OP compounds, and post-exposure therapy with anti-cholinergic drugs (atropine sulfate) to counteract the effects of excess acetylcholine and oximes (e.g., 2-PAM chloride) to reactivate OP-inhibited AChE. Oximes 359-365 acetylcholinesterase (Cartwright blood group) Homo sapiens 180-184 16429518-2 2005 The results demonstrate remarkable differences in the reactivation of inhibited brain AChE, depending on the oxime and species Oximes 109-114 acetylcholinesterase (Cartwright blood group) Homo sapiens 86-90 16429526-0 2005 Acetylcholinesterase mutants: oxime-assisted catalytic scavengers of organophosphonates. Oximes 30-35 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-20 16263103-7 2005 Accordingly, RBC-AChE appears to be a suitable parameter for judgment of oxime effectiveness at the neuromuscular junction, one of the most important targets for therapy where atropine is ineffective in OP-poisoning. Oximes 73-78 acetylcholinesterase (Cartwright blood group) Homo sapiens 17-21 16266695-1 2005 Standard treatment of poisoning by organophosphorus compounds (OP) includes the administration of an anti-muscarinic, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). Oximes 184-189 acetylcholinesterase (Cartwright blood group) Homo sapiens 143-163 16266695-1 2005 Standard treatment of poisoning by organophosphorus compounds (OP) includes the administration of an anti-muscarinic, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). Oximes 184-189 acetylcholinesterase (Cartwright blood group) Homo sapiens 165-169 16266695-7 2005 Reactivation of inhibited AChE is considered to be the main mechanism of action of oximes. Oximes 83-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-30 16266695-8 2005 Clinical data indicate that changes in erythrocyte AChE activity correlate to neuromuscular function indicating that interactions between AChE, inhibitor and oximes can be investigated in vitro with human erythrocyte AChE. Oximes 158-164 acetylcholinesterase (Cartwright blood group) Homo sapiens 51-55 16266695-8 2005 Clinical data indicate that changes in erythrocyte AChE activity correlate to neuromuscular function indicating that interactions between AChE, inhibitor and oximes can be investigated in vitro with human erythrocyte AChE. Oximes 158-164 acetylcholinesterase (Cartwright blood group) Homo sapiens 138-142 16266695-8 2005 Clinical data indicate that changes in erythrocyte AChE activity correlate to neuromuscular function indicating that interactions between AChE, inhibitor and oximes can be investigated in vitro with human erythrocyte AChE. Oximes 158-164 acetylcholinesterase (Cartwright blood group) Homo sapiens 138-142 16266695-9 2005 Different theoretical models were used for the evaluation of reactivating efficacy of oximes with nerve agent-inhibited human AChE and for estimating effective oxime concentrations. Oximes 86-92 acetylcholinesterase (Cartwright blood group) Homo sapiens 126-130 16266695-9 2005 Different theoretical models were used for the evaluation of reactivating efficacy of oximes with nerve agent-inhibited human AChE and for estimating effective oxime concentrations. Oximes 86-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 126-130 16429518-0 2005 Comparison of ability of some oximes to reactivate sarin-inhibited brain acetylcholinesterase from different species. Oximes 30-36 acetylcholinesterase (Cartwright blood group) Homo sapiens 73-93 15904945-2 2005 Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. Oximes 99-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 53-73 15904945-2 2005 Standard treatment with atropine and the established acetylcholinesterase (AChE) reactivators, obidoxime and pralidoxime, is considered to be ineffective with certain nerve agents due to low oxime effectiveness. Oximes 99-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-79 15904945-5 2005 Since reactivation of OP-inhibited AChE is considered to be the main mechanism of action of oximes, human erythrocyte AChE can be exploited to test the efficacy of new oximes. Oximes 92-98 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 15904945-6 2005 By combining enzyme kinetics (inhibition, reactivation, aging) with OP toxicokinetics and oxime pharmacokinetics a dynamic in vitro model was developed which allows the calculation of AChE activities at different scenarios. Oximes 90-95 acetylcholinesterase (Cartwright blood group) Homo sapiens 184-188 14985944-1 2004 The reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by oximes results inevitably in the formation of highly reactive phosphyloximes (POX), which may re-inhibit the enzyme. Oximes 82-88 acetylcholinesterase (Cartwright blood group) Homo sapiens 51-71 15654704-2 2005 Standard treatment involves administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. Oximes 71-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 88-108 15498514-0 2004 Kinetic analysis of interactions between human acetylcholinesterase, structurally different organophosphorus compounds and oximes. Oximes 123-129 acetylcholinesterase (Cartwright blood group) Homo sapiens 47-67 15498514-3 2004 Reactivators (oximes) of inhibited AChE are a mainstay of treatment, however, the commercially available compounds, obidoxime and pralidoxime, are considered to be rather ineffective against various nerve agents. Oximes 14-20 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 15498514-5 2004 However, the various interactions between AChE, OP and oximes can be investigated with human AChE which enables the direct assessment of oxime potency, thus excluding species differences. Oximes 55-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 93-97 15498514-5 2004 However, the various interactions between AChE, OP and oximes can be investigated with human AChE which enables the direct assessment of oxime potency, thus excluding species differences. Oximes 55-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 93-97 15498514-7 2004 The inhibitory potency of OPs, reactivating potency of oximes and spontaneous reactivation and aging were strongly affected by the structural characteristics of the OPs and of the phosphyl-AChE-complex. Oximes 55-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 189-193 15498514-9 2004 AChE inhibited by various phosphoramidates was mostly resistant towards reactivation by oximes while phosphonylated AChE was easily reactivated. Oximes 88-94 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-4 15514903-4 2004 Current treatments of patients poisoned with organophosphorus compounds include atropine (in order to protect muscarinic receptors), oximes (in order to accelerate the reactivation of the inhibited acetylcholinesterase) and benzodiazepines (in order to avoid convulsions). Oximes 133-139 acetylcholinesterase (Cartwright blood group) Homo sapiens 198-218 15379785-0 2004 Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase. Oximes 34-40 acetylcholinesterase (Cartwright blood group) Homo sapiens 76-96 15379785-1 2004 The efficacy of various oximes to reactivate acetylcholinesterase phosphorylated by tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) was tested by in vitro and in vivo methods. Oximes 24-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-65 16167316-2 2005 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators ("oximes") is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 84-90 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-61 16167316-2 2005 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators ("oximes") is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 84-90 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 16167316-2 2005 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators ("oximes") is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 84-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 41-61 16167316-2 2005 The standard treatment with atropine and acetylcholinesterase (AChE) reactivators ("oximes") is considered to be ineffective with certain nerve agents due to low oxime efficacy. Oximes 84-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 16119192-3 2005 Therefore, to better evaluate the efficacy of various oximes (pralidoxime, obidoxime, HI-6, K033) to reactivate brain acetylcholinesterase inhibited by sarin by in vitro methods, human, rat and pig brain acetylcholinesterase were used to calculate kinetic parameters for the reactivation. Oximes 54-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-138 16119193-6 2005 Three newly synthesized oximes achieved similar nucleophilicity at the similar pKa according to 4-PAM, which is very promising for using these derivatives as AChE reactivators. Oximes 24-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 158-162 15544060-2 2004 The new oxime K033 was found to be a more efficacious reactivator of sarin or cyclosarin-inhibited acetylcholinesterase than pralidoxime and obidoxime but it did not reach the efficacy of oxime HI-6 in the case of the inhibition of acetylcholinesterase by sarin or cyclosarin. Oximes 8-13 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-119 15544060-2 2004 The new oxime K033 was found to be a more efficacious reactivator of sarin or cyclosarin-inhibited acetylcholinesterase than pralidoxime and obidoxime but it did not reach the efficacy of oxime HI-6 in the case of the inhibition of acetylcholinesterase by sarin or cyclosarin. Oximes 8-13 acetylcholinesterase (Cartwright blood group) Homo sapiens 232-252 14985944-1 2004 The reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by oximes results inevitably in the formation of highly reactive phosphyloximes (POX), which may re-inhibit the enzyme. Oximes 82-88 acetylcholinesterase (Cartwright blood group) Homo sapiens 73-77 15568733-1 2004 The oxime K005 [1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide] for the reactivation of the enzyme acetylcholinesterase (AChE) inhibited by cyclosarin and VX was tested. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 110-130 14647978-5 2004 Human AChE inhibited by MFPCh, MFP beta Ch or MFPhCh was extremely resistant towards reactivation by oximes. Oximes 101-107 acetylcholinesterase (Cartwright blood group) Homo sapiens 6-10 14647978-8 2004 In conclusion, the unexpected results, i.e., high resistance of inhibited AChE towards oxime reactivation and aging, and much lower resistance towards spontaneous reactivation, calls for further experiments at a molecular level for a better understanding of the interactions among AChE, its inhibitors and reactivators. Oximes 87-92 acetylcholinesterase (Cartwright blood group) Homo sapiens 74-78 15095579-1 2004 The ability of the oxime HS-6 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride] to reactive in vitro the enzyme acetylcholinesterase inhibited by the nerve agent sarin [O-isopropylmethylfluorophosphonate] was evaluated. Oximes 19-24 acetylcholinesterase (Cartwright blood group) Homo sapiens 150-170 15095579-3 2004 The oxime HS-6 was an effective reactivator of sarin-inhibited AChE. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 15568733-1 2004 The oxime K005 [1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide] for the reactivation of the enzyme acetylcholinesterase (AChE) inhibited by cyclosarin and VX was tested. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 132-136 12242610-1 2002 Standard treatment of poisoning by organophosphates (OP) includes the administration of an antimuscarinic agent, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). Oximes 179-184 acetylcholinesterase (Cartwright blood group) Homo sapiens 138-158 12837382-4 2003 Further, they suggest that the improved performance of dimeric oximes is conferred by two-site binding with one oxime pointing toward the diisopropyl ester at the catalytic site of hAChE and the other anchored at the peripheral site. Oximes 63-69 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-186 12837382-4 2003 Further, they suggest that the improved performance of dimeric oximes is conferred by two-site binding with one oxime pointing toward the diisopropyl ester at the catalytic site of hAChE and the other anchored at the peripheral site. Oximes 63-68 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-186 15181665-7 2003 In vitro studies with human erythrocyte AChE, which is derived from the same single gene as synaptic AChE, revealed marked differences in the potency and efficacy of pralidoxime, obidoxime, HI 6 and HLo 7, the latter two oximes being considered particularly effective in nerve agent poisoning. Oximes 221-227 acetylcholinesterase (Cartwright blood group) Homo sapiens 40-44 15181665-7 2003 In vitro studies with human erythrocyte AChE, which is derived from the same single gene as synaptic AChE, revealed marked differences in the potency and efficacy of pralidoxime, obidoxime, HI 6 and HLo 7, the latter two oximes being considered particularly effective in nerve agent poisoning. Oximes 221-227 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-105 15181665-17 2003 AChE aging is particularly rapid with dimethyl phosphoryl compounds and may thwart the effective reactivation by oximes, particularly in suicidal poisoning with excessive doses. Oximes 113-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-4 12583695-1 2003 Early treatment of organophosphate (OP) poisoning with oximes results in reactivation of acetylcholinesterase and patient recovery. Oximes 55-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 89-109 12242610-1 2002 Standard treatment of poisoning by organophosphates (OP) includes the administration of an antimuscarinic agent, e.g. atropine, and of an acetylcholinesterase (AChE) reactivator (oxime). Oximes 179-184 acetylcholinesterase (Cartwright blood group) Homo sapiens 160-164 10817663-1 2000 The reactivation of organophosphate-inhibited acetylcholinesterase (AChE) by oximes inevitably results in the formation of highly reactive phosphoryloximes (POX), which are able to re-inhibit the enzyme. Oximes 77-83 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 12411190-1 2002 OBJECTIVE: Inhibition of acetylcholinesterase (AChE) in human brain caused by phoxim or phoxim oxon, their reactivation with oxime and aging of phosphorylated AChE were studied and compared in vitro. Oximes 125-130 acetylcholinesterase (Cartwright blood group) Homo sapiens 47-51 11805735-4 2002 The standard treatment consists of reactivation of the inhibited acetylcholinesterase with an oxime antidote and reversal of the biochemical effects of acetylcholine with atropine. Oximes 94-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 65-85 11978898-2 2002 Standard treatment involves the administration of intravenous atropine and an oxime to counter acetylcholinesterase inhibition at the synapse, but the usefulness of oximes is uncertain. Oximes 78-83 acetylcholinesterase (Cartwright blood group) Homo sapiens 95-115 11123973-3 2000 Electric eel acetylcholinesterase (EEAChE) was inhibited with the four stereoisomers of isomalathion, and rate constants for spontaneous and oxime-mediated reactivation (k(3)) were measured. Oximes 141-146 acetylcholinesterase (Cartwright blood group) Homo sapiens 13-33 11204553-6 2000 In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Oximes 136-142 acetylcholinesterase (Cartwright blood group) Homo sapiens 56-76 11204553-8 2000 These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. Oximes 176-181 acetylcholinesterase (Cartwright blood group) Homo sapiens 210-230 10801325-0 2000 Mechanism of oxime reactivation of acetylcholinesterase analyzed by chirality and mutagenesis. Oximes 13-18 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-55 10801325-2 2000 We have examined the reactivation of a series of resolved enantiomeric methylphosphonate conjugates of acetylcholinesterase by two oximes, 2-pralidoxime (2-PAM) and 1-(2"-hydroxyiminomethyl-1"-pyridinium)-3-(4"-carbamoyl-1-pyridinium) (HI-6). Oximes 131-137 acetylcholinesterase (Cartwright blood group) Homo sapiens 103-123 10817664-3 2000 Human plasma with the butyrylcholinesterase irreversibly blocked by soman was able to stimulate obidoxime-induced reactivation of concentrated erythrocyte acetylcholinesterase (Ery-AChE) to the same extent as was observed with a dilute preparation, suggesting phosphoryl oxime-destroying capacity. Oximes 100-105 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-185 10207609-2 1999 Since the oxime effectiveness is influenced not only by its reactivating potential but also by inhibition, aging and spontaneous reactivation kinetics, experiments were performed with human acetyl- (AChE) and butyrylcholinesterase (BChE) to determine the respective kinetic constants. Oximes 10-15 acetylcholinesterase (Cartwright blood group) Homo sapiens 199-203 10433700-0 1999 Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium. Oximes 11-16 acetylcholinesterase (Cartwright blood group) Homo sapiens 31-51 10433700-0 1999 Phosphoryl oxime inhibition of acetylcholinesterase during oxime reactivation is prevented by edrophonium. Oximes 59-64 acetylcholinesterase (Cartwright blood group) Homo sapiens 31-51 10433700-2 1999 This study with native, wild-type, and mutant recombinant DNA-expressed AChEs, each inhibited by representative OP compounds, establishes a relationship between edrophonium acceleration of oxime-induced reactivation of OP-AChE conjugates and phosphoryl oxime inhibition of the reactivated enzyme that occurs during reactivation by pyridinium oximes LuH6 and TMB4. Oximes 189-194 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-76 10433700-2 1999 This study with native, wild-type, and mutant recombinant DNA-expressed AChEs, each inhibited by representative OP compounds, establishes a relationship between edrophonium acceleration of oxime-induced reactivation of OP-AChE conjugates and phosphoryl oxime inhibition of the reactivated enzyme that occurs during reactivation by pyridinium oximes LuH6 and TMB4. Oximes 253-258 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-76 10433700-5 1999 However, phosphoryl oximes formed during the reactivation of the diethylphosphoryl-AChE conjugate were not sufficiently stable to be detected by (31)P NMR. Oximes 20-26 acetylcholinesterase (Cartwright blood group) Homo sapiens 83-87 10433700-7 1999 Reactivation of both ethoxy methylphosphonyl- and diethylphosphoryl-AChE by these two oximes was accelerated in the presence of rabbit serum paraoxonase, suggesting that organophosphorus hydrolase can hydrolyze phosphoryl oxime formed during the reactivation. Oximes 86-92 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 10433700-7 1999 Reactivation of both ethoxy methylphosphonyl- and diethylphosphoryl-AChE by these two oximes was accelerated in the presence of rabbit serum paraoxonase, suggesting that organophosphorus hydrolase can hydrolyze phosphoryl oxime formed during the reactivation. Oximes 86-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 10433700-8 1999 Our results emphasize that certain oximes, such as LuH6 and TMB4, if used in the treatment of OP pesticide poisoning may cause prolonged inhibition of AChE due to formation of phosphoryl oximes. Oximes 35-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 151-155 10433700-8 1999 Our results emphasize that certain oximes, such as LuH6 and TMB4, if used in the treatment of OP pesticide poisoning may cause prolonged inhibition of AChE due to formation of phosphoryl oximes. Oximes 187-193 acetylcholinesterase (Cartwright blood group) Homo sapiens 151-155 10704134-1 1999 Newly synthesized oximes, mono and bis imidazole derivatives, which promise to be more effective acetylcholinesterase reactivators than standard antidotes used, were investigated by spectrophotometric and electrochemical methods. Oximes 18-24 acetylcholinesterase (Cartwright blood group) Homo sapiens 97-117 10704134-3 1999 Dissociation constants of those oximes were also obtained by numerical treatment of overlapping equilibria, using the Lavendberg Marquardt least square method, and when compared with the same for some similar compounds, were found to be very effective acetylcholinesterase reactivators. Oximes 32-38 acetylcholinesterase (Cartwright blood group) Homo sapiens 252-272 10704134-5 1999 The results indicated that many oxime anions will be available at physiological pH 7.4 and a relative increased ability to reactivate inhibited acetylcholinesterase could be expected. Oximes 32-37 acetylcholinesterase (Cartwright blood group) Homo sapiens 144-164 10207609-7 1999 These data indicate that oximes may effectively reactivate human dimethylphosphoryl-AChE. Oximes 25-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 84-88 9635412-5 1998 Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. Oximes 27-32 acetylcholinesterase (Cartwright blood group) Homo sapiens 174-178 9547363-1 1998 Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by oximes is the primary reason for their effectiveness in the treatment of OP poisoning. Oximes 78-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-73 9547363-4 1998 To better understand the acceleration phenomenon, we examined ligand modulations of oxime-induced reactivation of methylphosphonylated AChE using 7-(methylethoxyphosphinyloxy)-1-methylquinolinium iodide and fetal bovine serum AChE. Oximes 84-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 135-139 9547363-4 1998 To better understand the acceleration phenomenon, we examined ligand modulations of oxime-induced reactivation of methylphosphonylated AChE using 7-(methylethoxyphosphinyloxy)-1-methylquinolinium iodide and fetal bovine serum AChE. Oximes 84-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 226-230 9547363-9 1998 Propidium slowed the reactivation of 7-(methylethoxyphosphinyloxy)-1- methylquinolinium iodide-inhibited AChE by all oximes. Oximes 117-123 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-109 9635412-5 1998 Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. Oximes 129-135 acetylcholinesterase (Cartwright blood group) Homo sapiens 152-172 9635412-5 1998 Among compounds containing oxime functional groups only OPAB, having longer methylene chain and being more lipophylic than other oximes usually used in acetylcholinesterase (AChE) reactivation studies, was effective in decreasing the rate of aging on DFP-inhibited NTE. Oximes 129-135 acetylcholinesterase (Cartwright blood group) Homo sapiens 174-178 8619258-0 1996 Oxime-induced reactivation of acetylcholinesterase inhibited by phosphoramidates. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 30-50 9587020-4 1998 Since oximes are believed to act primarily through reactivation of inhibited acetylcholinesterase (AChE) and erythrocyte AChE is regarded to be a good marker for the synaptic enzyme, the reactivating potency can be investigated with human erythrocyte AChE in vitro. Oximes 6-12 acetylcholinesterase (Cartwright blood group) Homo sapiens 77-97 9587020-4 1998 Since oximes are believed to act primarily through reactivation of inhibited acetylcholinesterase (AChE) and erythrocyte AChE is regarded to be a good marker for the synaptic enzyme, the reactivating potency can be investigated with human erythrocyte AChE in vitro. Oximes 6-12 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-103 9587020-5 1998 The present study was undertaken to evaluate the ability of various oximes at concentrations therapeutically relevant in humans to reactivate human erythrocyte AChE inhibited by different nerve agents. Oximes 68-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 160-164 9587020-8 1998 The reactivation of human AChE by oximes was dependent on the organophosphate used. Oximes 34-40 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-30 9448738-0 1998 Combined effect of organophosphorus hydrolase and oxime on the reactivation rate of diethylphosphoryl-acetylcholinesterase conjugates. Oximes 50-55 acetylcholinesterase (Cartwright blood group) Homo sapiens 102-122 9209694-1 1997 The efficiency of newly synthesized oxime derivatives of quinuclidinium were tested in vitro on soman inhibited acetylcholinesterase (AChE) of human erythrocytes and in vivo using soman poisoned mice. Oximes 36-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 112-132 9209694-1 1997 The efficiency of newly synthesized oxime derivatives of quinuclidinium were tested in vitro on soman inhibited acetylcholinesterase (AChE) of human erythrocytes and in vivo using soman poisoned mice. Oximes 36-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 134-138 8794905-0 1996 Interactions of oxime reactivators with diethylphosphoryl adducts of human acetylcholinesterase and its mutant derivatives. Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-95 9292287-6 1997 Obidoxime turned out to be the most potent and most efficacious oxime in reactivating AChE inhibited by various classes of OP insecticides and tabun. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 86-90 9292287-10 1997 However, in suicidal mega-dose poisoning, oximes, even at optimal plasma concentrations, may be unable to cope with the fast re-inhibition of reactivated AChE in the first days following intoxication. Oximes 42-48 acetylcholinesterase (Cartwright blood group) Homo sapiens 154-158 9292288-3 1997 By virtue of in vitro findings and theoretical considerations we concluded in the preceding paper that oximes should preferably be administered by continuous infusion following an initial bolus dose for as long as reactivation of inhibited acetylcholinesterase (AChE) can be expected. Oximes 103-109 acetylcholinesterase (Cartwright blood group) Homo sapiens 240-260 9292288-3 1997 By virtue of in vitro findings and theoretical considerations we concluded in the preceding paper that oximes should preferably be administered by continuous infusion following an initial bolus dose for as long as reactivation of inhibited acetylcholinesterase (AChE) can be expected. Oximes 103-109 acetylcholinesterase (Cartwright blood group) Homo sapiens 262-266 8783813-0 1996 Reactivation by various oximes of human erythrocyte acetylcholinesterase inhibited by different organophosphorus compounds. Oximes 24-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 52-72 8911635-2 1996 Although oximes have been designed to reactivate the inhibited acetylcholinesterase (AChE), clinical experience has indicated that they are not always very effective as reactivators and at this very moment none of them can be regarded as a broad-spectrum antidote. Oximes 9-15 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-83 8911635-2 1996 Although oximes have been designed to reactivate the inhibited acetylcholinesterase (AChE), clinical experience has indicated that they are not always very effective as reactivators and at this very moment none of them can be regarded as a broad-spectrum antidote. Oximes 9-15 acetylcholinesterase (Cartwright blood group) Homo sapiens 85-89 8783813-5 1996 The oximes significantly, but not completely, reactivated organophosphate inhibited AChE. Oximes 4-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 84-88 8134223-13 1994 In vitro, oximes reactivated acetylcholinesterase inhibited with paraoxon, whereas no significant effect of oximes on carbamylated enzyme activity was observed. Oximes 10-16 acetylcholinesterase (Cartwright blood group) Homo sapiens 29-49 8750900-4 1995 With HI 6 alone, the portion of AChE activity which could be reactivated 25 min after the start of ageing decreased rapidly with the delay of the oxime addition (100% of the original activity at immediate addition), the half-life being approximately 2.5 min. Oximes 146-151 acetylcholinesterase (Cartwright blood group) Homo sapiens 32-36 7799993-8 1995 In humans, the efficacy of oximes in AChE reactivation can be determined rapidly using electrophysiologic studies. Oximes 27-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 37-41 7857205-0 1994 In vitro oxime-induced reactivation of various molecular forms of soman-inhibited acetylcholinesterase in striated muscle from rat, monkey and human. Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 82-102 7857205-3 1994 In the Pre-Post mode the oxime effects would result from a combination of not only shielding of acetylcholinesterase from soman inhibition but also from immediate reactivation of soman-inhibited acetylcholinesterase. Oximes 25-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 96-116 7857205-3 1994 In the Pre-Post mode the oxime effects would result from a combination of not only shielding of acetylcholinesterase from soman inhibition but also from immediate reactivation of soman-inhibited acetylcholinesterase. Oximes 25-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 195-215 7857205-9 1994 Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. Oximes 17-22 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-83 7857205-9 1994 Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. Oximes 17-22 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-138 7857205-9 1994 Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. Oximes 17-22 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-138 1412499-4 1992 We have found that the inhibition of both eel acetylcholinesterase (eel AChE, EC 3.1.1.7) and human serum cholinesterase (human BuChE, EC 3.1.1.8) by carbaryl was enhanced by several oximes. Oximes 183-189 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-76 8344000-1 1993 O-Ethyl-O-4-nitrophenylphosphoramidate is a short-acting anticholinesterase and a possible candidate for a prophylactic agent against nerve agents since human acetylcholinesterase inhibited by this agent undergoes rapid spontaneous reactivation which can be accelerated further, if necessary, by treatment with oximes. Oximes 311-317 acetylcholinesterase (Cartwright blood group) Homo sapiens 159-179 1733041-0 1992 Central activity of acetylcholinesterase oxime reactivators. Oximes 41-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 20-40 1733041-1 1992 The ability of various oximes to antagonize the sarin-induced hypothermia and reactivate phosphorylated acetylcholinesterase was used as an indicator of the central activity of oximes. Oximes 23-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 104-124 1890690-6 1991 The oxime HI-6 reactivated soman phosphonylated enzymes to a considerably greater extent than other oximes, and FBS AChE was notably more responsive to HI-6 than to other oximes. Oximes 171-177 acetylcholinesterase (Cartwright blood group) Homo sapiens 116-120 1890690-8 1991 In general, oxime potency and some rank order varied with each inhibitor and with each AChE, although there was some similarity in oxime rank order between the two mammalian AChEs. Oximes 12-17 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-91 2362084-0 1990 Oxime-induced reactivation of acetylcholinesterase inhibited by organophosphinates. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 30-50 2362084-1 1990 The comparative potency of oximes for reactivation of inhibited eel acetylcholinesterase (AChE) in vitro is dependent on the organophosphinate inhibitor. Oximes 27-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-88 2362084-1 1990 The comparative potency of oximes for reactivation of inhibited eel acetylcholinesterase (AChE) in vitro is dependent on the organophosphinate inhibitor. Oximes 27-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 90-94 2362084-3 1990 This work was done to identify more clearly the nature of phosphinylated AChE with regard to oxime reactivation potency and the potential of phosphinates as pretreatment drugs to protect AChE against organophosphonate poisoning. Oximes 93-98 acetylcholinesterase (Cartwright blood group) Homo sapiens 73-77 2362084-6 1990 Incubation of the inhibited enzyme (I-AChE) at 25 degrees C was with 0.30 microM oxime for PMP, 3.0 microM oxime for sarin and CPMP and 100 microM oxime for the two remaining phosphinates. Oximes 81-86 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-42 2362084-6 1990 Incubation of the inhibited enzyme (I-AChE) at 25 degrees C was with 0.30 microM oxime for PMP, 3.0 microM oxime for sarin and CPMP and 100 microM oxime for the two remaining phosphinates. Oximes 107-112 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-42 2362084-6 1990 Incubation of the inhibited enzyme (I-AChE) at 25 degrees C was with 0.30 microM oxime for PMP, 3.0 microM oxime for sarin and CPMP and 100 microM oxime for the two remaining phosphinates. Oximes 107-112 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-42 34558680-0 2022 Caged Oxime Reactivators Designed for the Light Control of Acetylcholinesterase Reactivation. Oximes 6-11 acetylcholinesterase (Cartwright blood group) Homo sapiens 59-79 33588047-3 2021 We report the QSAR regression model for the estimation of potency of a set of 94 structurally diverse compounds (oximes, N-hydroxyiminoacetamides, 4-aminoquinolines and flavonoids) to inhibit AChE, pKi (AChE). Oximes 113-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 192-196 33588047-3 2021 We report the QSAR regression model for the estimation of potency of a set of 94 structurally diverse compounds (oximes, N-hydroxyiminoacetamides, 4-aminoquinolines and flavonoids) to inhibit AChE, pKi (AChE). Oximes 113-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 203-207 34558680-2 2022 Here, we describe synthesis, photochemical properties, and biochemical activities of two caged oxime compounds applied in the photocontrolled reactivation of the AChE inactivated by reactive organophosphate. Oximes 95-100 acetylcholinesterase (Cartwright blood group) Homo sapiens 162-166 34558680-3 2022 Each of these consists of a photocleavable coumarin cage tethered to a known oxime reactivator for AChE that belongs in an either 2-(hydroxyimino)acetamide or pyridiniumaldoxime class. Oximes 77-82 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-103 34671741-0 2021 Dual acting oximes designed for therapeutic decontamination of reactive organophosphates via catalytic inactivation and acetylcholinesterase reactivation. Oximes 12-18 acetylcholinesterase (Cartwright blood group) Homo sapiens 120-140 34324828-5 2021 We also demonstrate the dissociation of organophosphate (OP)-conjugated dimers is reversed by structurally diverse oximes 2PAM, HI6 or RS194B, as demonstrated by SAXS of diethylphosphoryl-hAChE. Oximes 115-121 acetylcholinesterase (Cartwright blood group) Homo sapiens 188-193 34324828-6 2021 However, binding of oximes to the native ligand-free hAChE, binding of high-affinity reversible ligands, or formation of a SP-sarin-hAChE conjugate had no effect on homodimerization. Oximes 20-26 acetylcholinesterase (Cartwright blood group) Homo sapiens 53-58 34541552-3 2021 Reactivation of inhibited hAChE can be achieved with nucleophilic antidotes, such as oximes. Oximes 85-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-31 34541552-5 2021 Here we report X-ray structures of hAChE conjugated with a reversible covalent inhibitor 4K-TMA (4K-TMA:hAChE) at 2.8 A resolution and of 4K-TMA:hAChE conjugate with oxime reactivator methoxime, MMB4 (4K-TMA:hAChE:MMB4) at 2.6 A resolution, both at physiologically relevant room temperature, as well as cryo-crystallographic structure of 4K-TMA:hAChE at 2.4 A resolution. Oximes 166-171 acetylcholinesterase (Cartwright blood group) Homo sapiens 145-150 34671741-5 2021 This library was screened by enzyme assays performed with human and electric eel subtypes of OP-inactivated AChE, which led to identifying three oxime leads that displayed significant enhancements in reactivation activity comparable to 2-PAM. Oximes 145-150 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-112 35164361-1 2022 A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. Oximes 32-37 acetylcholinesterase (Cartwright blood group) Homo sapiens 123-143 34330964-2 2021 The current standard treatment against their effects relies on the use of small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Oximes 95-101 acetylcholinesterase (Cartwright blood group) Homo sapiens 131-151 34330964-2 2021 The current standard treatment against their effects relies on the use of small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Oximes 95-101 acetylcholinesterase (Cartwright blood group) Homo sapiens 153-157 35489467-0 2022 Theoretical assessment of the performances of commercial oximes on the reactivation of acetylcholinesterase inhibited by the nerve agent A-242 (novichok). Oximes 57-63 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-107 35526478-2 2022 Compared to non-halogenated oximes, halogenated oximes showed lower pKa of the oxime group (fluorinated < chlorinated < non-halogenated) along with higher level of oximate anion formation at the physiological pH, and had a higher binding affinity of both AChE and BChE. Oximes 28-34 acetylcholinesterase (Cartwright blood group) Homo sapiens 255-259 35526478-2 2022 Compared to non-halogenated oximes, halogenated oximes showed lower pKa of the oxime group (fluorinated < chlorinated < non-halogenated) along with higher level of oximate anion formation at the physiological pH, and had a higher binding affinity of both AChE and BChE. Oximes 48-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 255-259 35526478-2 2022 Compared to non-halogenated oximes, halogenated oximes showed lower pKa of the oxime group (fluorinated < chlorinated < non-halogenated) along with higher level of oximate anion formation at the physiological pH, and had a higher binding affinity of both AChE and BChE. Oximes 79-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 255-259 35526478-6 2022 The advantage of halogen substituents in the stabilization of oxime in a position optimal for in-line nucleophilic attack were confirmed by extensive molecular modelling of pre-reactivation complexes between the analogue oximes and phosphorylated AChE and BChE. Oximes 62-67 acetylcholinesterase (Cartwright blood group) Homo sapiens 247-251 35526478-6 2022 The advantage of halogen substituents in the stabilization of oxime in a position optimal for in-line nucleophilic attack were confirmed by extensive molecular modelling of pre-reactivation complexes between the analogue oximes and phosphorylated AChE and BChE. Oximes 221-227 acetylcholinesterase (Cartwright blood group) Homo sapiens 247-251 35527825-2 2022 We developed a novel QSAR regression model for estimating potency to inhibit AChE, pK i, on a set of 75 structurally different compounds including oximes, N-hydroxyiminoacetamides, 4-aminoquinolines and flavonoids. Oximes 147-153 acetylcholinesterase (Cartwright blood group) Homo sapiens 77-81 3345199-1 1988 Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. Oximes 162-168 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-20 2917984-2 1989 With the exception of the conjugate formed from reaction of AchE with RP-cycloheptyl methylphosphonyl thiocholine, all enantiomeric conjugates underwent oxime reactivation at rates that were within 2-3-fold of each other. Oximes 153-158 acetylcholinesterase (Cartwright blood group) Homo sapiens 60-64 2596267-1 1989 It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. Oximes 40-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 60-80 2596267-1 1989 It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. Oximes 40-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 82-86 2596267-1 1989 It has been reported recently that some oximes reactivating acetylcholinesterase (AChE) exhibit concomitant ganglion-blocking effects which presumably could contribute independently to their powerful antidotal action in organophosphate inhibitor (OPI) poisoning, thus mimicking some unrelated substances which are effective antidotes without reactivating AChE. Oximes 40-46 acetylcholinesterase (Cartwright blood group) Homo sapiens 355-359 3345199-1 1988 Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. Oximes 162-168 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 33563155-14 2022 Further, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. Oximes 85-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 119-123 3972833-6 1985 NBD-aminoethyl methylphosphono-acetylcholinesterase undergoes oxime-induced as well as spontaneous reactivation at rates that are 3.6 and 35 times faster, respectively, than the corresponding rates measured for the NBD-aminopentyl conjugate. Oximes 62-67 acetylcholinesterase (Cartwright blood group) Homo sapiens 31-51 6497906-0 1984 The reactivation by oximes of phosphonylated acetylcholinesterase: the possible erroneous interpretation of reactivating potency. Oximes 20-26 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-65 6497906-1 1984 A comparative study of the reactivation by two oximes of acetylcholinesterase inhibited by several organophosphates has been made, with particular reference to the dependence of the degree of reactivation produced by an oxime (reactivating potency) upon the concentration of inhibited enzyme. Oximes 47-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 57-77 6497906-1 1984 A comparative study of the reactivation by two oximes of acetylcholinesterase inhibited by several organophosphates has been made, with particular reference to the dependence of the degree of reactivation produced by an oxime (reactivating potency) upon the concentration of inhibited enzyme. Oximes 47-52 acetylcholinesterase (Cartwright blood group) Homo sapiens 57-77 20487840-4 1981 Rapid hydrolysis of phosphonylated acetylcholinesterase can be brought about by oximes, but dealkylation of the phosphonyl group on the enzyme (known as ageing) renders the inhibited enzyme insensitive to oximes. Oximes 80-86 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-55 497002-0 1979 Some adjuncts to oxime-atropine therapy for organophosphate intoxication--their effects on acetylcholinesterase. Oximes 17-22 acetylcholinesterase (Cartwright blood group) Homo sapiens 91-111 1015993-0 1976 Potential acetylcholinesterase reactivators: oxime and amidoxime derivatives. Oximes 45-50 acetylcholinesterase (Cartwright blood group) Homo sapiens 10-30 33592259-3 2021 Oximes are a critical piece to the therapeutic regimen which remove the OP from the inhibited AChE and restore normal cholinergic function. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 94-98 3746817-5 1986 In this series, varying R substituents on the aryl ring produced compounds with oxime pKa values from 6.8 to 8.0, optimum for an AChE reactivator. Oximes 80-85 acetylcholinesterase (Cartwright blood group) Homo sapiens 129-133 3954783-3 1986 The rates of inhibition of AChE by these phosphylated oximes and the parent (and related) organophosphates have also been measured. Oximes 54-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 27-31 7426043-0 1980 Reactivation of acetylcholinesterase inhibited by 1,2,2"-trimethylpropyl methylphosphonofluoridate (soman) with HI-6 and related oximes. Oximes 129-135 acetylcholinesterase (Cartwright blood group) Homo sapiens 16-36 435080-5 1979 The oximes with a hydroxyiminomethyl group in position 4 in the pyridinium ring were good reactivators of both phosphorylated and phosphonylated acetylcholinesterase. Oximes 4-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 145-165 34019427-1 2021 Oxime-based molecules are used for the treatment of patients to reactivate acetylcholinesterase (AChE) function after organophosphate intoxication. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-95 34019427-1 2021 Oxime-based molecules are used for the treatment of patients to reactivate acetylcholinesterase (AChE) function after organophosphate intoxication. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 97-101 33990679-2 2021 Oxime reactivators of organophosphate (OP)-inhibited acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) serve as antidotes toward poisoning by OPNAs. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-79 32899591-7 2020 Comparing theoretical and experimental data, it is possible to notice that the oxime, in most cases, showed better reactivation percentages at higher concentrations, with the best result for the reactivation of the AChE-VX adduct. Oximes 79-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 215-219 32334495-3 2021 When AChE is inhibited by OPs, its reactivation can be usually performed through cationic oximes. Oximes 90-96 acetylcholinesterase (Cartwright blood group) Homo sapiens 5-9 32835730-6 2020 A major drawback of currently available oxime reactivators is their inability to reactivate AChE in the central nervous system (CNS) as they are unable to cross the blood-brain barrier. Oximes 40-45 acetylcholinesterase (Cartwright blood group) Homo sapiens 92-96 32544483-0 2020 Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 57-77 32544483-0 2020 Oxime-mediated reactivation of organophosphate-inhibited acetylcholinesterase with emphasis on centrally-active oximes. Oximes 112-118 acetylcholinesterase (Cartwright blood group) Homo sapiens 57-77 32388435-0 2020 Design, synthesis and evaluation of novel nonquaternary and 3 non-oxime reactivators for acetylcholinesterase inhibited by organophosphates. Oximes 66-71 acetylcholinesterase (Cartwright blood group) Homo sapiens 89-109 32388435-4 2020 It was also found that some non-oxime derivatives of Mannich phenols displayed obvious reactivation potency for VX, sarin and pesticides inhibited hAChE even in very low concentration. Oximes 32-37 acetylcholinesterase (Cartwright blood group) Homo sapiens 147-152 32454005-0 2020 Synthesis and in vitro evaluation of novel non-oximes for the reactivation of nerve agent inhibited human acetylcholinesterase. Oximes 47-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-126 32454005-1 2020 Since several decades oximes have been used as part of treatment of nerve agent intoxication with the aim to restore the biological function of the enzyme acetylcholinesterase after its covalent inhibition by organophosphorus compounds such as pesticides and nerve agents. Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 155-175 32388435-1 2020 A new series of novel nonquaternary conjugates and non-oxime reactivators for reactivation of both nerve agents and pesticides inhibited hAChE were described in this paper. Oximes 55-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 137-142 32333945-0 2020 Efficient detoxification of nerve agents by oxime-assisted reactivation of acetylcholinesterase mutants. Oximes 44-49 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-95 32267631-1 2020 Oximes like pralidoxime (2-PAM), obidoxime (Obi) and HI-6 are the only currently available therapeutics to reactivate inhibited acetylcholinesterase (AChE) in case of intoxications with organophosphorus (OP) compounds. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 128-148 32267631-1 2020 Oximes like pralidoxime (2-PAM), obidoxime (Obi) and HI-6 are the only currently available therapeutics to reactivate inhibited acetylcholinesterase (AChE) in case of intoxications with organophosphorus (OP) compounds. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 150-154 32333945-5 2020 Therefore, this review focuses on oxime-assisted catalysis by AChE mutants that provides a potential means for degradation of organophosphates in the plasma before reaching the cellular target site. Oximes 34-39 acetylcholinesterase (Cartwright blood group) Homo sapiens 62-66 31830555-2 2020 Current post-exposure nerve agent treatment includes atropine to treat overstimulation at muscarinic synapses, a benzodiazepine anti-convulsant, and an oxime to restore the function of AChE. Oximes 152-157 acetylcholinesterase (Cartwright blood group) Homo sapiens 185-189 32380126-3 2020 Oximes reactivate AChE in both the peripheral nervous system and the CNS. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 18-22 32105443-2 2020 Oxime reactivators of AChE are used in medical practice in the treatment of nerve agent poisoning, but the search for novel improved reactivators with central activity is an ongoing pursuit. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 32086265-8 2020 In one case report, AChE activity increased after oxime administration indicating therapeutic success whereas BChE activity did not. Oximes 50-55 acetylcholinesterase (Cartwright blood group) Homo sapiens 20-24 32019865-0 2020 Rational design, synthesis and evaluation of uncharged, "smart" bis-oxime antidotes of organophosphate-inhibited human acetylcholinesterase. Oximes 64-73 acetylcholinesterase (Cartwright blood group) Homo sapiens 119-139 32019865-5 2020 On the basis of X-ray structures of a CNS-penetrating reactivator, monoxime RS194B, reversibly bound to native and venomous agent X (VX)-inhibited human AChE (hAChE), here we created seven uncharged acetamido bis-oximes as candidate antidotes. Oximes 199-219 acetylcholinesterase (Cartwright blood group) Homo sapiens 153-157 32178264-4 2020 Within the most outstanding reactivators, the substances denominated oximes stand out, showing good performance for reactivating AChE and restoring the normal synaptic acetylcholine (ACh) levels. Oximes 69-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 129-133 31074292-3 2019 To investigate these interactions, theoretical results from docking were first compared with experimental data of hybrid 5C, 4-PA, and two commercial oximes, on the reactivation of human AChE (HssAChE) inhibited by VX. Oximes 150-156 acetylcholinesterase (Cartwright blood group) Homo sapiens 187-191 31022458-1 2020 There is a unique in vivo interplay involving the mechanism of inactivation of acetylcholinesterase (AChE) by toxic organophosphorus (OP) compounds and the restoration of AChE activity by oxime antidotes. Oximes 188-193 acetylcholinesterase (Cartwright blood group) Homo sapiens 171-175 31022458-2 2020 OP compounds form covalent adducts to this critical enzyme target and oximes are introduced to directly displace the OP from AChE. Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 125-129 32175496-0 2020 Molecular Modeling Study of Uncharged Oximes Compared to HI-6 and 2-PAM Inside Human AChE Sarin and VX Conjugates. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 85-89 32175496-3 2020 HI-6 and 2-PAM are cationic oximes proved to be effective for the reactivation of AChE inhibited by the nerve agents VX and sarin (GB). Oximes 28-34 acetylcholinesterase (Cartwright blood group) Homo sapiens 82-86 32175496-5 2020 Uncharged oximes appear as an interesting alternative to solve this problem, but the development and enhancement of more efficient uncharged oximes capable of reactivating human AChE is still necessary. Oximes 10-16 acetylcholinesterase (Cartwright blood group) Homo sapiens 178-182 32175496-5 2020 Uncharged oximes appear as an interesting alternative to solve this problem, but the development and enhancement of more efficient uncharged oximes capable of reactivating human AChE is still necessary. Oximes 141-147 acetylcholinesterase (Cartwright blood group) Homo sapiens 178-182 32175496-8 2020 The uncharged oximes showed different behaviors, especially RS194B, which presented stability inside AChE-VX, but presented free binding energy lower than cationic oximes, suggesting that structural alterations could favor its interactions with these complexes. Oximes 14-20 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-105 32175496-9 2020 In contrast, HI-6 and 2-PAM showed higher affinities with more negative binding energy values and larger contribution of the amino acid Asp74, demonstrating the importance of the quaternary nitrogen to the affinity and interaction of oximes with AChE-GB and AChE-VX conjugates. Oximes 234-240 acetylcholinesterase (Cartwright blood group) Homo sapiens 246-250 30950246-3 2019 The current antidotes are oxime-based drugs that can regenerate the AChE catalytic activity. Oximes 26-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 31276662-4 2019 In vitro studies showed higher intrinsic toxicities of both oximes than 2-PAM for AChE. Oximes 60-66 acetylcholinesterase (Cartwright blood group) Homo sapiens 82-86 31176713-7 2019 Successful solution of the new room temperature 3.2 A resolution structure of BW284c51*hAChE complex from large P31 crystals enables us to proceed with studying room temperature structures of lower affinity complexes, such as oxime reactivators bound to hAChE, where temperature-related conformational diversity could be expected in both oxime and hAChE, which could lead to better informed structure-based design under conditions approaching physiological temperature. Oximes 226-231 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-92 31176713-7 2019 Successful solution of the new room temperature 3.2 A resolution structure of BW284c51*hAChE complex from large P31 crystals enables us to proceed with studying room temperature structures of lower affinity complexes, such as oxime reactivators bound to hAChE, where temperature-related conformational diversity could be expected in both oxime and hAChE, which could lead to better informed structure-based design under conditions approaching physiological temperature. Oximes 338-343 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-92 31138650-0 2019 Productive reorientation of a bound oxime reactivator revealed in room temperature X-ray structures of native and VX-inhibited human acetylcholinesterase. Oximes 36-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 133-153 31138650-4 2019 Current antidotes, including oxime reactivators that attack the OP-AChE conjugate to free the active enzyme, are inefficient. Oximes 29-34 acetylcholinesterase (Cartwright blood group) Homo sapiens 67-71 31138650-6 2019 Here, we present room temperature X-ray structures of native and VX-phosphonylated hAChE with an imidazole-based oxime reactivator, RS-170B. Oximes 113-118 acetylcholinesterase (Cartwright blood group) Homo sapiens 83-88 31112674-5 2019 The central compartment is readily accessible by the OPs which are lipophilic bullets that can easily cross the BBB, whereas first-line therapeutics, namely oxime-based AChE reactivators and atropine, do not cross or do so rather slowly. Oximes 157-162 acetylcholinesterase (Cartwright blood group) Homo sapiens 169-173 31112674-6 2019 The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 30-34 31112674-6 2019 The limitation of oxime-based AChE reactivators can be ascribed to their chemical nature, bearing a positive charge which is essential either for their AChE affinity or their reactivating potency. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 152-156 30858091-12 2019 However, the oxime HI-6 as potent reactivator of cyclosarin-inhibited AChE was not able to prevent the FPDc prolongation in this model. Oximes 13-18 acetylcholinesterase (Cartwright blood group) Homo sapiens 70-74 31276662-3 2019 Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (POX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM). Oximes 68-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 134-138 30444932-5 2019 Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 54-74 30978400-2 2019 Currently used therapy in counteracting excessive cholinergic stimulation consists of a muscarinic antagonist (atropine) and an oxime reactivator of inhibited AChE, but the classical oximes are particularly ineffective in counteracting tabun exposure. Oximes 128-133 acetylcholinesterase (Cartwright blood group) Homo sapiens 159-163 30978400-3 2019 In a recent publication (Kovarik et al., 2019), we showed that several oximes prepared by the Huisgen 1,3 dipolar cycloaddition and related precursors efficiently reactivate the tabun-AChE conjugate. Oximes 71-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 184-188 30978400-7 2019 Indeed, after initial screening of the triazole oxime library and its precursors for the reactivation efficacy on Y337A and Y337A/F338A human AChE mutants, we found potentially active oxime-mutant enzyme pairs capable of degrading tabun in cycles of inhibition and reactivation. Oximes 48-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 142-146 30444932-5 2019 Oxime nucleophiles can reactivate select OP-inhibited acetylcholinesterase (AChE). Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 76-80 30458057-0 2019 Reversal of Tabun Toxicity Enabled by a Triazole-Annulated Oxime Library-Reactivators of Acetylcholinesterase. Oximes 59-64 acetylcholinesterase (Cartwright blood group) Homo sapiens 89-109 30682493-0 2019 Oxidative stress induced by oxime reactivators of acetylcholinesterase in vitro. Oximes 28-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 50-70 30458057-1 2019 Acetylcholinesterase (AChE), an enzyme that degrades the neurotransmitter acetylcholine, when covalently inhibited by organophosphorus compounds (OPs), such as nerve agents and pesticides, can be reactivated by oximes. Oximes 211-217 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-20 30458057-1 2019 Acetylcholinesterase (AChE), an enzyme that degrades the neurotransmitter acetylcholine, when covalently inhibited by organophosphorus compounds (OPs), such as nerve agents and pesticides, can be reactivated by oximes. Oximes 211-217 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 30458057-5 2019 We identified several oximes with significantly improved in vitro reactivating potential for tabun-inhibited human AChE, and in vivo antidotal efficacies in tabun-exposed mice. Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 115-119 30362667-1 2018 The current standard therapy to counteract organophosphate intoxication is not effective in equal measure against all types of organophosphorus compounds (OPCs), as the outcome of oxime-induced reactivation of inactivated acetylcholinesterase (AChE) strongly depends on the particular OPC. Oximes 180-185 acetylcholinesterase (Cartwright blood group) Homo sapiens 222-242 30362667-1 2018 The current standard therapy to counteract organophosphate intoxication is not effective in equal measure against all types of organophosphorus compounds (OPCs), as the outcome of oxime-induced reactivation of inactivated acetylcholinesterase (AChE) strongly depends on the particular OPC. Oximes 180-185 acetylcholinesterase (Cartwright blood group) Homo sapiens 244-248 30312685-0 2018 Interactions between acetylcholinesterase, toxic organophosphorus compounds and a short series of structurally related non-oxime reactivators: Analysis of reactivation and inhibition kinetics in vitro. Oximes 123-128 acetylcholinesterase (Cartwright blood group) Homo sapiens 21-41 30312685-2 2018 Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). Oximes 83-89 acetylcholinesterase (Cartwright blood group) Homo sapiens 64-68 30312685-2 2018 Insufficient efficacy of the standard therapy with atropine and AChE reactivators (oximes) against certain OP initiated synthesis of novel non-oxime reactivators basing on the common structure 4-amino-2-((diethylamino)methyl)phenol (ADOC). Oximes 83-88 acetylcholinesterase (Cartwright blood group) Homo sapiens 64-68 30424582-0 2018 Molecular Modeling and In Vitro Studies of a Neutral Oxime as a Potential Reactivator for Acetylcholinesterase Inhibited by Paraoxon. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 90-110 30265992-3 2018 The in vitro reactivation experiment for pesticides inhibited hAChE of these new synthesized oximes were conducted for the first time. Oximes 93-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 62-67 30265992-5 2018 It was found that introduction of peripheral site ligands could increase oximes" binding affinity for inhibited hAChE in most cases, which resulted in greater reactivation ability. Oximes 73-79 acetylcholinesterase (Cartwright blood group) Homo sapiens 112-117 30125110-3 2018 A promising reactivator based on tetrahydroacridine linked to a nonquaternary oxime is also an undesired submicromolar reversible inhibitor of AChE. Oximes 78-83 acetylcholinesterase (Cartwright blood group) Homo sapiens 143-147 30096649-0 2018 Discovery of a potent non-oxime reactivator of nerve agent inhibited human acetylcholinesterase. Oximes 26-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 75-95 30096649-3 2018 The presently fielded oximes reactivate OP-inhibited AChE by liberating the phosphylated serine. Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 53-57 30096649-6 2018 Recently, a number of non-oxime compounds was discovered in which the 4-amino-2-((diethylamino)methyl)phenol (ADOC) motif proved to be able to reactivate OP-inhibited AChE to some extent. Oximes 26-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 167-171 30096649-8 2018 We here disclose that one of those compounds showed a remarkable ability to reactivate OP-inhibited hAChE in vitro and that it is the most potent non-oxime reported to date. Oximes 150-155 acetylcholinesterase (Cartwright blood group) Homo sapiens 100-105 28993240-1 2018 Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. Oximes 192-198 acetylcholinesterase (Cartwright blood group) Homo sapiens 0-20 28993240-1 2018 Acetylcholinesterase (AChE) inhibited by the organophosphorus nerve (OP) agent soman underlies a spontaneous and extremely rapid dealkylation ("aging") reaction which prevents reactivation by oximes. Oximes 192-198 acetylcholinesterase (Cartwright blood group) Homo sapiens 22-26 28993240-7 2018 In conclusion, the results of the present study indicate a negligible reactivation of soman-inhibited AChE by oximes at conditions simulating the in vivo poisoning by soman. Oximes 110-116 acetylcholinesterase (Cartwright blood group) Homo sapiens 102-106 29180286-0 2018 The estimation of oxime efficiency is affected by the experimental design of phosphylated acetylcholinesterase reactivation. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 90-110 29180286-3 2018 The endeavor of many chemists to find more efficient reactivators resulted in thousands of newly-designed and synthesized oximes-potential reactivators of AChE. Oximes 122-128 acetylcholinesterase (Cartwright blood group) Homo sapiens 155-159 30110162-3 2018 Phosphylation of acetylcholinesterase produces two adducts, an initial neutral adduct that can be reactivated with oxime nucleophiles, and a subsequent monoanionic adduct (called aged acetylcholinesterase) which has proven over two generations to be impervious to reactivation. Oximes 115-120 acetylcholinesterase (Cartwright blood group) Homo sapiens 17-37 29772260-0 2018 Oxime-assisted reactivation of tabun-inhibited acetylcholinesterase analysed by active site mutations. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 47-67 29772260-1 2018 The antidotal property of oximes is attributed to their ability to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP) such as pesticides and nerve warfare agents. Oximes 26-32 acetylcholinesterase (Cartwright blood group) Homo sapiens 78-98 29772260-1 2018 The antidotal property of oximes is attributed to their ability to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP) such as pesticides and nerve warfare agents. Oximes 26-32 acetylcholinesterase (Cartwright blood group) Homo sapiens 100-104 29614332-3 2018 Treatment for toxicity due to OPC exposure has been largely focused on the reactivation of AChE by oxime-based compounds via direct nucleophilic attack on the phosphorous center. Oximes 99-104 acetylcholinesterase (Cartwright blood group) Homo sapiens 91-95 29980922-0 2018 Influence of gauche effect on uncharged oxime reactivators for the reactivation of tabun-inhibited AChE: quantum chemical and steered molecular dynamics studies. Oximes 40-45 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-103 29980922-1 2018 The neutral oxime reactivator RS194B with a seven-membered ring has shown better efficacy towards the tabun-inhibited AChE than that of RS69N with a six-membered ring and RS41A with a five-membered ring. Oximes 12-17 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-122 28446076-2 2018 Some oximes such HI6 as 2-PAM are nucleophiles that are capable to reactivate inhibited human AChE under some conditions. Oximes 5-11 acetylcholinesterase (Cartwright blood group) Homo sapiens 94-98 28446076-0 2018 Behavior of uncharged oximes compared to HI6 and 2-PAM in the human AChE-tabun conjugate: a molecular modeling approach. Oximes 22-28 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 29773682-0 2018 Water structure changes in oxime-mediated reactivation process of phosphorylated human acetylcholinesterase. Oximes 27-32 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-107 29773682-2 2018 To investigate oximate water structure changes in this reaction, reactivation of paraoxon-inhibited human acetylcholinesterase (AChE) was performed by the oxime asoxime (HI-6) at different pH in the presence and absence of lyotropic salts: a neutral salt (NaCl), a strong chaotropic salt (LiSCN) and strong kosmotropic salts (ammonium sulphate and phosphate HPO42-). Oximes 155-160 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-126 29773682-2 2018 To investigate oximate water structure changes in this reaction, reactivation of paraoxon-inhibited human acetylcholinesterase (AChE) was performed by the oxime asoxime (HI-6) at different pH in the presence and absence of lyotropic salts: a neutral salt (NaCl), a strong chaotropic salt (LiSCN) and strong kosmotropic salts (ammonium sulphate and phosphate HPO42-). Oximes 155-160 acetylcholinesterase (Cartwright blood group) Homo sapiens 128-132 29735900-4 2018 Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). Oximes 12-18 acetylcholinesterase (Cartwright blood group) Homo sapiens 189-193 29735900-4 2018 Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). Oximes 12-17 acetylcholinesterase (Cartwright blood group) Homo sapiens 189-193 28722512-5 2018 In silico the molecular interactions between AChE and oximes were examined and binding energies were assessed. Oximes 54-60 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-49 29553731-0 2018 Dynamic Mechanism of a Fluorinated Oxime Reactivator Unbinding from AChE Gorge in Polarizable Water. Oximes 35-40 acetylcholinesterase (Cartwright blood group) Homo sapiens 68-72 29577198-3 2018 Oxime-induced reactivation of acetylcholinesterase was most pronounced in dipyroxime and toxogonin: parameters of the kinetics of reduction of the phosphorylated enzyme differed by more than 2 times from the values received with the use of other reactivators. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 30-50 28722512-7 2018 In vitro the intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 147-151 28722512-7 2018 In vitro the intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 56-60 31723659-4 2017 Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Oximes 113-119 acetylcholinesterase (Cartwright blood group) Homo sapiens 14-34 31723659-4 2017 Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Oximes 173-179 acetylcholinesterase (Cartwright blood group) Homo sapiens 14-34 28646405-0 2017 Revealing the importance of linkers in K-series oxime reactivators for tabun-inhibited AChE using quantum chemical, docking and SMD studies. Oximes 48-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-91 29201079-0 2017 Docking Studies, Synthesis, and In-vitro Evaluation of Novel Oximes Based on Nitrones as Reactivators of Inhibited Acetylcholinesterase. Oximes 61-67 acetylcholinesterase (Cartwright blood group) Homo sapiens 115-135 28542985-6 2017 Oximes poorly reactivate AChE inhibited by phosphoramidates. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 25-29 27582056-9 2016 Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. Oximes 37-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 110-114 31294152-5 2017 Oximes are compounds that reactivate Acetylcholinesterase (AChE), a regulatory enzyme responsible for the transmission of nerve impulses, which is one of the molecular targets most vulnerable to neurotoxic agents. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 37-57 31294152-5 2017 Oximes are compounds that reactivate Acetylcholinesterase (AChE), a regulatory enzyme responsible for the transmission of nerve impulses, which is one of the molecular targets most vulnerable to neurotoxic agents. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 59-63 27358236-3 2017 An interim solution could be the administration of external AChE or BChE from blood products to augment pseudocatalytic scavenging with slower but clinically approved oximes to decrease nerve agent concentrations in the body. Oximes 167-173 acetylcholinesterase (Cartwright blood group) Homo sapiens 60-64 28165084-0 2017 Unbinding of fluorinated oxime drug from the AChE gorge in polarizable water: a well-tempered metadynamics study. Oximes 25-30 acetylcholinesterase (Cartwright blood group) Homo sapiens 45-49 26612005-0 2016 Docking and molecular dynamics studies of peripheral site ligand-oximes as reactivators of sarin-inhibited human acetylcholinesterase. Oximes 65-71 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-133 26612005-1 2016 In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Oximes 116-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 184-188 26612005-1 2016 In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Oximes 116-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 162-182 27125761-2 2016 The need for an effective treatment of OP poisoning resulted in the implementation of a combination therapy with the muscarinic receptor antagonist atropine and an oxime for the reactivation of OP-inhibited acetylcholinesterase (AChE). Oximes 164-169 acetylcholinesterase (Cartwright blood group) Homo sapiens 229-233 27062893-0 2016 Probing the activity of a non-oxime reactivator for acetylcholinesterase inhibited by organophosphorus nerve agents. Oximes 30-35 acetylcholinesterase (Cartwright blood group) Homo sapiens 52-72 27062893-2 2016 2PAM reactivates nerve agent-inhibited AChE via direct nucleophilic attack by the oxime moiety on the phosphorus center of the bound nerve agent. Oximes 82-87 acetylcholinesterase (Cartwright blood group) Homo sapiens 39-43 27238725-1 2016 Within this study, we designed and synthesized four new oxime compounds of the N-substituted 2-hydroxyiminoacetamide structure and evaluated their interactions with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Oximes 56-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 165-185 27238725-1 2016 Within this study, we designed and synthesized four new oxime compounds of the N-substituted 2-hydroxyiminoacetamide structure and evaluated their interactions with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Oximes 56-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 187-191 27125761-6 2016 Multiple in vitro and in vivo studies investigated the potential of oximes to reactivate OP-inhibited AChE and to reverse OP-induced cholinergic signs. Oximes 68-74 acetylcholinesterase (Cartwright blood group) Homo sapiens 102-106 27494215-0 2016 Biological Testing of Organophosphorus-Inactivated Acetylcholinesterase Oxime Reactivators Identified via Virtual Screening. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 51-71 27693733-7 2016 The cholinesterases displayed a binding affinity for these derivatives in a mumolar range no matter the substituent on their rings which was in accordance with the molecular modelling results showing a similar binding pattern for all oximes within the active site of both AChE and BChE. Oximes 234-240 acetylcholinesterase (Cartwright blood group) Homo sapiens 272-276 27494215-4 2016 In order to find new starting points for the development of oxime-containing therapeutic reactivators and to increase our base of knowledge, we have employed a combination of computational and experimental procedures to identify additional compounds with the real or potential ability to reactivate AChE while augmenting and complementing current knowledge. Oximes 60-65 acetylcholinesterase (Cartwright blood group) Homo sapiens 299-303 27450532-6 2016 In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. Oximes 38-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-123 27371941-0 2016 Limitations in current acetylcholinesterase structure-based design of oxime antidotes for organophosphate poisoning. Oximes 70-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 23-43 27191504-4 2016 We have solved structures of human acetylcholinesterase in different states in complex with the organophosphate insecticide, paraoxon, and oximes. Oximes 139-145 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-55 27191504-8 2016 Ternary structures of paraoxon-inhibited human acetylcholinesterase in complex with the oximes HI6 and 2-PAM reveals relatively poor positioning for reactivation. Oximes 88-94 acetylcholinesterase (Cartwright blood group) Homo sapiens 47-67 27371941-2 2016 Catalytically inactive OP-AChE conjugates formed between the active-center serine and phosphorus of OPs can, in principle, be reactivated by nucleophilic oxime antidotes. Oximes 154-159 acetylcholinesterase (Cartwright blood group) Homo sapiens 26-30 27371941-3 2016 Antidote efficacy is limited by the structural diversity of OP-AChE conjugates resulting from differences in the structure of the conjugated OP, the different active-center volumes they occupy when conjugated to the active-center serine of AChE, and the distinct chemical characteristics of both OPs and oximes documented in numerous X-ray structures of OP-conjugated AChEs. Oximes 304-310 acetylcholinesterase (Cartwright blood group) Homo sapiens 63-67 27371941-4 2016 Efforts to improve oxime reactivation efficacy by AChE structure-based enhancement of oxime structure have yielded only limited success. Oximes 19-24 acetylcholinesterase (Cartwright blood group) Homo sapiens 50-54 27371941-4 2016 Efforts to improve oxime reactivation efficacy by AChE structure-based enhancement of oxime structure have yielded only limited success. Oximes 86-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 50-54 27371941-5 2016 We outline here the potential limitations of available AChE X-ray structures that preclude an accurate prediction of oxime structures, which are necessary for association in the OP-AChE gorge and nucleophilic attack of the OP-conjugated phosphorus. Oximes 117-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 55-59 27371941-5 2016 We outline here the potential limitations of available AChE X-ray structures that preclude an accurate prediction of oxime structures, which are necessary for association in the OP-AChE gorge and nucleophilic attack of the OP-conjugated phosphorus. Oximes 117-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-185 27000635-2 2016 The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. Oximes 141-146 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-125 27327269-6 2016 For postaging treatment, realkylation of aged AChE by appropriate alkylators may pave the way for oxime treatment by neutralizing the oxyanion at the active site of aged AChE. Oximes 98-103 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-50 27327269-6 2016 For postaging treatment, realkylation of aged AChE by appropriate alkylators may pave the way for oxime treatment by neutralizing the oxyanion at the active site of aged AChE. Oximes 98-103 acetylcholinesterase (Cartwright blood group) Homo sapiens 170-174 27101948-0 2016 Oxime-mediated in vitro reactivation kinetic analysis of organophosphates-inhibited human and electric eel acetylcholinesterase. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 107-127 27101948-9 2016 Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 187-191 27101948-9 2016 Studies stipulated that butene-linked oximes consisting of different functional moieties are good reactivators and found to have better efficacy to reactivate nerve agent-inhibited human AChE in comparison to eel AChE. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 213-217 27000635-2 2016 The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. Oximes 141-146 acetylcholinesterase (Cartwright blood group) Homo sapiens 127-131 27000635-2 2016 The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. Oximes 141-146 acetylcholinesterase (Cartwright blood group) Homo sapiens 193-197 26879641-2 2016 We have examined the structural features of the tabun-conjugated AChE complex with an oxime reactivator, Ortho-7, to provide a strategy for designing new and efficient reactivators. Oximes 86-91 acetylcholinesterase (Cartwright blood group) Homo sapiens 65-69 26468911-0 2015 Protein-Drug Interactions with Effective Polarization in Polarizable Water: Oxime Unbinding from AChE Gorge. Oximes 76-81 acetylcholinesterase (Cartwright blood group) Homo sapiens 97-101 26809136-4 2016 The ortho-hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. Oximes 25-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 71-75 25743373-2 2016 Inhibited AChE can be reactivated by cleavage of the Ser-phosphorus bond either spontaneously or through a reaction with nucleophilic agents, such as oximes. Oximes 150-156 acetylcholinesterase (Cartwright blood group) Homo sapiens 10-14 25743373-5 2016 Here, our goal was to study oxime reactivation and aging reactions of human AChE inhibited by mipafox or a sarin analog (Flu-MPs, fluorescent methylphosphonate). Oximes 28-33 acetylcholinesterase (Cartwright blood group) Homo sapiens 76-80 26210933-1 2016 The limited effectiveness of the established oximes obidoxime and pralidoxime resulted in ongoing research on novel oximes for the reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP). Oximes 45-51 acetylcholinesterase (Cartwright blood group) Homo sapiens 169-173 26210933-1 2016 The limited effectiveness of the established oximes obidoxime and pralidoxime resulted in ongoing research on novel oximes for the reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP). Oximes 116-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 147-167 26210933-1 2016 The limited effectiveness of the established oximes obidoxime and pralidoxime resulted in ongoing research on novel oximes for the reactivation of acetylcholinesterase (AChE) inhibited by organophosphorus compounds (OP). Oximes 116-122 acetylcholinesterase (Cartwright blood group) Homo sapiens 169-173 26210933-4 2016 Several oximes with superior reactivating potency towards selective OP-AChE conjugates were identified but none of the tested oximes can be considered as a broad spectrum reactivator. Oximes 8-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 71-75 26851641-1 2016 Standard therapy of poisoning by organophosphorus compounds (OP) is a combined administration of an anti-muscarinic drug (e.g. atropine) and an oxime as reactivator of inhibited acetylcholinesterase (AChE). Oximes 144-149 acetylcholinesterase (Cartwright blood group) Homo sapiens 178-198 26851641-1 2016 Standard therapy of poisoning by organophosphorus compounds (OP) is a combined administration of an anti-muscarinic drug (e.g. atropine) and an oxime as reactivator of inhibited acetylcholinesterase (AChE). Oximes 144-149 acetylcholinesterase (Cartwright blood group) Homo sapiens 200-204 27153754-0 2016 Reactivation of nerve agent-inhibited human acetylcholinesterase by obidoxime, HI-6 and obidoxime+HI-6: Kinetic in vitro study with simulated nerve agent toxicokinetics and oxime pharmacokinetics. Oximes 72-77 acetylcholinesterase (Cartwright blood group) Homo sapiens 44-64 27153754-3 2016 To investigate the ability of obidoxime, HI-6 and the combination of both oximes to reactivate inhibited human AChE in the presence of sarin, cyclosarin or tabun we adopted a dynamic in vitro model with real-time and continuous determination of AChE activity to simulate inhalation nerve agent exposure and intramuscular oxime administration. Oximes 74-80 acetylcholinesterase (Cartwright blood group) Homo sapiens 111-115 27153754-5 2016 The oxime-induced reactivation of inhibited human AChE in the presence of nerve agents is markedly impaired and the combination of obidoxime and HI-6 had no additive effect but could broaden the spectrum. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 50-54 26747974-2 2016 Both oximes are very potent reactivators of organophosphate-inhibited AChE. Oximes 5-11 acetylcholinesterase (Cartwright blood group) Homo sapiens 70-74 26368669-1 2015 Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. Oximes 88-94 acetylcholinesterase (Cartwright blood group) Homo sapiens 16-36 26368669-1 2015 Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. Oximes 88-94 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-42 26368669-1 2015 Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. Oximes 88-93 acetylcholinesterase (Cartwright blood group) Homo sapiens 16-36 26368669-1 2015 Tabun-inhibited acetylcholinesterase (AChE) is rather resistant towards reactivation by oximes in vitro while in vivo experiments showed some protection of animals poisoned by this chemical warfare nerve agent after treatment with an oxime and atropine. Oximes 88-93 acetylcholinesterase (Cartwright blood group) Homo sapiens 38-42 26368669-2 2015 In addition, AChE inhibited by close tabun analogues, N,N-diethyltabun and N,N-di-n-propyltabun was completely resistant towards reactivation by oximes. Oximes 145-151 acetylcholinesterase (Cartwright blood group) Homo sapiens 13-17 26368669-3 2015 In order to get more insight into potential mechanisms of this oxime resistance experiments with these toxic agents and the oximes obidoxime, 2-PAM, MMB-4 and HI-6 were performed utilizing a dynamic model with real-time determination of AChE activity. Oximes 63-68 acetylcholinesterase (Cartwright blood group) Homo sapiens 237-241 26368669-8 2015 These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE. Oximes 161-167 acetylcholinesterase (Cartwright blood group) Homo sapiens 121-125 26368669-8 2015 These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE. Oximes 161-167 acetylcholinesterase (Cartwright blood group) Homo sapiens 298-302 26368669-8 2015 These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE. Oximes 161-166 acetylcholinesterase (Cartwright blood group) Homo sapiens 121-125 26368669-8 2015 These data give further support to the assumption that an interaction of tabun with residues in the active site gorge of AChE prevents effective reactivation by oximes, a mechanism which may also be the reason for the total oxime resistance of N,N-diethyl- and N,N-di-n-propyltabun-inhibited human AChE. Oximes 161-166 acetylcholinesterase (Cartwright blood group) Homo sapiens 298-302 26468911-2 2015 We present oxime (HI-6) unbinding from the active site gorge of AChE, known to be strongly influenced by intermolecular cation-pi, hydrogen bridge (HB) and water bridge (WB) interactions and by molecular simulations with effective polarization in polarizable mean-field model of TIP3P water. Oximes 11-16 acetylcholinesterase (Cartwright blood group) Homo sapiens 64-68 25407587-0 2015 Molecular modeling and in vitro reactivation study between the oxime BI-6 and acetylcholinesterase inhibited by different nerve agents. Oximes 63-68 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-98 25451328-1 2015 In this study, we employed site-directed mutagenesis to understand the role of amino acids in the gorge in oxime-induced reactivation of nerve agent-inhibited human (Hu) acetylcholinesterase (AChE). Oximes 107-112 acetylcholinesterase (Cartwright blood group) Homo sapiens 192-196 26070418-7 2015 However, the synthesized oximes showed marginal reactivation efficacies in case of tabun inhibited hAChE. Oximes 25-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-104 25835984-2 2015 Oxime antidotes commonly used to reactivate organophosphate inhibited AChE are ineffective against soman, while the efficacy of the recommended nerve agent bioscavenger butyrylcholinesterase is limited by strictly stoichiometric scavenging. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 70-74 25240274-6 2014 This effect was not observed when incubating highly diluted AChE with oximes. Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 60-64 24805972-0 2015 Oxime-dipeptides as anticholinesterase, reactivator of phosphonylated-serine of AChE catalytic triad: probing the mechanistic insight by MM-GBSA, dynamics simulations and DFT analysis. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 80-84 25845909-1 2015 Oxime K203 seems to be the most promising oxime in case of reactivation of tabun-inhibited acetylcholinesterase (AChE). Oximes 42-47 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-117 25522658-0 2015 Effect of reversible ligands on oxime-induced reactivation of sarin- and cyclosarin-inhibited human acetylcholinesterase. Oximes 32-37 acetylcholinesterase (Cartwright blood group) Homo sapiens 100-120 25522658-4 2015 Hereby, oxime-induced reactivation of OP-inhibited non-human AChE was reported to be accelerated by different AChE-ligands. Oximes 8-13 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-65 25522658-4 2015 Hereby, oxime-induced reactivation of OP-inhibited non-human AChE was reported to be accelerated by different AChE-ligands. Oximes 8-13 acetylcholinesterase (Cartwright blood group) Homo sapiens 110-114 25522658-5 2015 To investigate this concept with AChE from human source, the inhibitory potency, binding properties and the potential enhancement of oxime-induced reactivation of OP-inhibited AChE by structurally different AChE-ligands was assessed. Oximes 133-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 33-37 25522658-5 2015 To investigate this concept with AChE from human source, the inhibitory potency, binding properties and the potential enhancement of oxime-induced reactivation of OP-inhibited AChE by structurally different AChE-ligands was assessed. Oximes 133-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 176-180 25522658-5 2015 To investigate this concept with AChE from human source, the inhibitory potency, binding properties and the potential enhancement of oxime-induced reactivation of OP-inhibited AChE by structurally different AChE-ligands was assessed. Oximes 133-138 acetylcholinesterase (Cartwright blood group) Homo sapiens 176-180 25522658-6 2015 Several ligands competed with the oxime for the AChE binding-site impairing reactivation of OP-inhibited AChE whereas a markedly accelerated reactivation of sarin-inhibited enzyme by obidoxime was recorded in the presence of edrophonium, galanthamine and donepezil. Oximes 34-39 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-52 25522658-6 2015 Several ligands competed with the oxime for the AChE binding-site impairing reactivation of OP-inhibited AChE whereas a markedly accelerated reactivation of sarin-inhibited enzyme by obidoxime was recorded in the presence of edrophonium, galanthamine and donepezil. Oximes 34-39 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-109 25373357-0 2015 Relationships between the antidotal efficacy and structure, PK/PD parameters and bio-relevant molecular descriptors of AChE reactivating oximes: inclusion and integration to biopharmaceutical classification systems. Oximes 137-143 acetylcholinesterase (Cartwright blood group) Homo sapiens 119-123 25373357-1 2015 INTRODUCTION: The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability to achieve the nucleophilic attack and their affinity for the anionic center of the intact/inhibited AChE. Oximes 41-47 acetylcholinesterase (Cartwright blood group) Homo sapiens 93-113 25373357-1 2015 INTRODUCTION: The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability to achieve the nucleophilic attack and their affinity for the anionic center of the intact/inhibited AChE. Oximes 41-47 acetylcholinesterase (Cartwright blood group) Homo sapiens 115-119 25373357-1 2015 INTRODUCTION: The therapeutic outcome of oximes used as reactivators of phosphorylated human acetylcholinesterase (AChE) is influenced, among other factors, by their biological distribution, their in vivo ability to achieve the nucleophilic attack and their affinity for the anionic center of the intact/inhibited AChE. Oximes 41-47 acetylcholinesterase (Cartwright blood group) Homo sapiens 314-318 25373357-5 2015 EXPERT OPINION: The structural differences of the organophosphorus compounds (OP) and the available oximes reactivators of OP-inhibited AChE generate distinct toxicokinetic or PK profiles. Oximes 100-106 acetylcholinesterase (Cartwright blood group) Homo sapiens 136-140 25479380-1 2014 For three random splits, one-variable models of oximes reactivation of sarin inhibited acetylcholinesterase (logarithm of the AChE reactivation percentage by oximes with concentration of 0.001 M) have been calculated with CORAL software. Oximes 48-54 acetylcholinesterase (Cartwright blood group) Homo sapiens 126-130 24549829-0 2014 Unbinding free energy of acetylcholinesterase bound oxime drugs along the gorge pathway from metadynamics-umbrella sampling investigation. Oximes 52-57 acetylcholinesterase (Cartwright blood group) Homo sapiens 25-45 25218671-0 2014 Quantum chemical and steered molecular dynamics studies for one pot solution to reactivate aged acetylcholinesterase with alkylator oxime. Oximes 132-137 acetylcholinesterase (Cartwright blood group) Homo sapiens 96-116 25218671-1 2014 Dimethyl(pyridin-2-yl)sulfonium based oxime has been designed to reverse the aging process of organophosphorus inhibited AChE and to reactivate the aged-AChE adduct. Oximes 38-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 121-125 25218671-1 2014 Dimethyl(pyridin-2-yl)sulfonium based oxime has been designed to reverse the aging process of organophosphorus inhibited AChE and to reactivate the aged-AChE adduct. Oximes 38-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 153-157 25218671-5 2014 The free enzyme can be liberated from the inhibited acetylcholinesterase with the sulfonium compound decorated with an oxime group to avoid the administration of oxime drugs separately. Oximes 119-124 acetylcholinesterase (Cartwright blood group) Homo sapiens 52-72 25218671-5 2014 The free enzyme can be liberated from the inhibited acetylcholinesterase with the sulfonium compound decorated with an oxime group to avoid the administration of oxime drugs separately. Oximes 162-167 acetylcholinesterase (Cartwright blood group) Homo sapiens 52-72 25218671-12 2014 The computational study suggests that the newly designed oxime is a potential candidate to reactivate the aged-AChE adduct. Oximes 57-62 acetylcholinesterase (Cartwright blood group) Homo sapiens 111-115 25190468-1 2014 The search of proficient oximes as reactivators of irreversibly inhibited-AChE by organophosphate poisoning necessitates an appropriate assessment of their physicochemical properties and reactivation kinetics. Oximes 25-31 acetylcholinesterase (Cartwright blood group) Homo sapiens 74-78 25190468-4 2014 Further the tested oximes were screened through in vitro reactivation kinetics against paraoxon-inhibited AChE. Oximes 19-25 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-110 23735753-9 2013 On the other hand pralidoxime, an oxime, reactivating acetylcholinesterase (AChE) after organophosphate poisoning, induced population spike recovery after DFP exposure in the presence of bradykinin and Lys-des-Arg(9)-bradykinin. Oximes 24-29 acetylcholinesterase (Cartwright blood group) Homo sapiens 76-80 24964273-3 2014 Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. Oximes 90-95 acetylcholinesterase (Cartwright blood group) Homo sapiens 137-141 24599312-3 2014 Moreover, these oximes also exhibit a good ability to reactivate VX-, tabun- and paraoxon-inhibited human AChE. Oximes 16-22 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-110 24258240-0 2014 Oxime-type acetylcholinesterase reactivators in pregnancy: an overview. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 11-31 24344993-5 2014 In this work, we evaluated the affinity and reactivity of oximes with activity already reported against AChE inhibited by the OP chemical warfare agent ciclosarin, with MmAChE and HsAChE active sites inhibited by the CB pesticide carbofuran. Oximes 58-64 acetylcholinesterase (Cartwright blood group) Homo sapiens 104-108 23962483-0 2013 Investigation of kinetic interactions between approved oximes and human acetylcholinesterase inhibited by pesticide carbamates. Oximes 55-61 acetylcholinesterase (Cartwright blood group) Homo sapiens 72-92 23962483-4 2013 Therefore, we performed an in vitro kinetic study to investigate the effect of clinically used oximes on carbamoylation and decarbamoylation of human AChE. Oximes 95-101 acetylcholinesterase (Cartwright blood group) Homo sapiens 150-154 24312449-7 2013 The calculated activation barriers support the superiority of neutral oximes for the activation of tabun-inhibited AChE compared to charged oximes. Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 115-119 24312449-9 2013 Docking studies revealed that the poor binding affinity of simple neutral oxime drugs such as 3-hydroxy-2-pyridinealdoxime inside the active-site gorge of AChE was significantly augmented with the addition of neutral peripheral units compared to conventional charged peripheral sites. Oximes 74-79 acetylcholinesterase (Cartwright blood group) Homo sapiens 155-159 24345352-1 2014 Reactivation of organophosphate (OP) inhibited acetylcholinesterase (AChE) by oximes is inadequate against various OP nerve agents known till date owing to their diverse structural features. Oximes 78-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 69-73 24345352-3 2014 The efficacy of oxime reactivators is estimated through different in vitro and in vivo models using AChE from various sources against structurally different OPs. Oximes 16-21 acetylcholinesterase (Cartwright blood group) Homo sapiens 100-104 24345352-7 2014 The enhanced reactivation efficacy of oximes may be attributed to the optimal length of xylene linker which facilitates appropriate positioning of carbamoyl function to the peripheral anionic site (PAS) and extending the oxime moiety to the active site of AChE. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 256-260 24345352-7 2014 The enhanced reactivation efficacy of oximes may be attributed to the optimal length of xylene linker which facilitates appropriate positioning of carbamoyl function to the peripheral anionic site (PAS) and extending the oxime moiety to the active site of AChE. Oximes 38-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 256-260 24057572-1 2014 Great efforts have been undertaken in the last decades to develop new oximes to reactivate acetylcholinesterase inhibited by organophosphorus compounds (OP). Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 91-111 24443939-0 2014 Exploring the physicochemical properties of oxime-reactivation therapeutics for cyclosarin, sarin, tabun, and VX inactivated acetylcholinesterase. Oximes 44-49 acetylcholinesterase (Cartwright blood group) Homo sapiens 125-145 24443939-2 2014 The reactivation of OP-inactivated AChE is dependent on the OP conjugate, and commonly a specific oxime is better at reactivating a specific OP conjugate than several diverse OP conjugates. Oximes 98-103 acetylcholinesterase (Cartwright blood group) Homo sapiens 35-39 24443939-8 2014 The reactivation of AChE inactivated with either cyclosarin or tabun requires the oxime therapeutic to possess an overall polar-positive surface area. Oximes 82-87 acetylcholinesterase (Cartwright blood group) Homo sapiens 20-24 24443939-9 2014 Oxime therapeutics for the reactivation of sarin-inactivated AChE are conformationally dependent while oxime reverse therapeutics for VX require a compact region with a highly hydrophilic region and two positively charged pyridine rings. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-65 24157926-2 2013 Standard treatment by administration of atropine and oximes, e.g., obidoxime or pralidoxime, focuses on antagonism of mAChRs and reactivation of AChE, whereas nicotinic malfunction is not directly treated. Oximes 53-59 acetylcholinesterase (Cartwright blood group) Homo sapiens 145-149 23789829-0 2013 In silico pharmacophore modeling on known pyridinium oxime reactivators of cyclosarin (GF) inhibited AChE to Aid discovery of potential, more efficacious novel non-oxime reactivators. Oximes 53-58 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-105 23789829-3 2013 The model was generated from published experimental percentage reactivation data on oximes as changes of AChE/BuChE activities in the whole blood after cyclosarin intoxication and administration. Oximes 84-90 acetylcholinesterase (Cartwright blood group) Homo sapiens 105-109 23789829-6 2013 Furthermore, from virtual screening of two commercial databases, Maybridge and ChemNavigator using map-fitting of the model led us to identify two new non-oxime compounds showing reactivation efficacy within 10-fold range of 2-PAM for DFP-inhibited AChE. Oximes 155-160 acetylcholinesterase (Cartwright blood group) Homo sapiens 249-253 23534424-1 2013 BACKGROUND: Extreme efforts are made for the structural diversification of oximes used as AChE reactivators. Oximes 75-81 acetylcholinesterase (Cartwright blood group) Homo sapiens 90-94 23959117-0 2013 Oximes: inhibitors of human recombinant acetylcholinesterase. Oximes 0-6 acetylcholinesterase (Cartwright blood group) Homo sapiens 40-60 23959117-3 2013 Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. Oximes 107-113 acetylcholinesterase (Cartwright blood group) Homo sapiens 127-131 23959117-4 2013 However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. Oximes 9-15 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-52 23959117-5 2013 The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Oximes 50-55 acetylcholinesterase (Cartwright blood group) Homo sapiens 113-117 22960624-0 2013 Centrally acting oximes in reactivation of tabun-phosphoramidated AChE. Oximes 17-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 66-70 22982773-0 2013 A common mechanism for resistance to oxime reactivation of acetylcholinesterase inhibited by organophosphorus compounds. Oximes 37-42 acetylcholinesterase (Cartwright blood group) Homo sapiens 59-79 22982773-1 2013 Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 186-206 22982773-1 2013 Administration of oxime therapy is currently the standard approach used to reverse the acute toxicity of organophosphorus (OP) compounds, which is usually attributed to OP inhibition of acetylcholinesterase (AChE). Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 208-212 22982773-2 2013 Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 48-52 22982773-2 2013 Rate constants for reactivation of OP-inhibited AChE by even the best oximes, such as HI-6 and obidoxime, can vary >100-fold between OP-AChE conjugates that are easily reactivated and those that are difficult to reactivate. Oximes 70-76 acetylcholinesterase (Cartwright blood group) Homo sapiens 139-143 22982773-3 2013 To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues. Oximes 39-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 164-168 22982773-3 2013 To gain a better understanding of this oxime specificity problem for future design of improved reactivators, we conducted a QSAR analysis for oxime reactivation of AChE inhibited by OP agents and their analogues. Oximes 142-147 acetylcholinesterase (Cartwright blood group) Homo sapiens 164-168 22982773-4 2013 Our objective was to identify common mechanism(s) among OP-AChE conjugates of phosphates, phosphonates and phosphoramidates that result in resistance to oxime reactivation. Oximes 153-158 acetylcholinesterase (Cartwright blood group) Homo sapiens 59-63 22982773-5 2013 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 40-44 22982773-5 2013 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 196-200 22982773-5 2013 Our evaluation of oxime reactivation of AChE inhibited by a sarin analogue, O-methyl isopropylphosphonofluoridate, or a cyclosarin analogue, O-methyl cyclohexylphosphonofluoridate, indicated that AChE inhibited by these analogues was at least 70-fold more difficult to reactivate than AChE inhibited by sarin or cyclosarin. Oximes 18-23 acetylcholinesterase (Cartwright blood group) Homo sapiens 196-200 23111374-4 2013 In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. Oximes 47-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 159-179 23111374-4 2013 In this study, a series of seven new uncharged oximes reactivators have been synthesized and their in vitro ability to reactivate VX and tabun-inhibited human acetylcholinesterase (hAChE) has been evaluated. Oximes 47-53 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-186 22827894-0 2013 Structural requirements for effective oximes--evaluation of kinetic in vitro data with phosphylated human AChE and structurally different oximes. Oximes 38-44 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-110 22827894-1 2013 Treatment of poisoning by various organophosphorus (OP) nerve agents with established acetylcholinesterase (AChE) reactivators (oximes) is insufficient. Oximes 128-134 acetylcholinesterase (Cartwright blood group) Homo sapiens 86-106 22827894-1 2013 Treatment of poisoning by various organophosphorus (OP) nerve agents with established acetylcholinesterase (AChE) reactivators (oximes) is insufficient. Oximes 128-134 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-112 22827894-4 2013 The crucial mechanism of action of oximes is the reactivation of phosphylated AChE. Oximes 35-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 78-82 22827894-6 2013 It was tempting to evaluate the reactivation kinetics of a series of oximes with various OP inhibitors performed under identical experimental conditions in order to get insight into structural requirements for adequate affinity and reactivity towards inhibited AChE. Oximes 69-75 acetylcholinesterase (Cartwright blood group) Homo sapiens 261-265 22827894-7 2013 The determination of reactivation rate constants with bispyridinium oximes having different linkers, bearing oxime group(s) at different positions and having in part additional substituents revealed that (a) the reactivating potency was dependent on the position of the oxime groups and of additional substituents, (b) small modifications of the oxime structure had an in part marked effect on the kinetic properties and (c) no single oxime had an adequate reactivating potency with AChE inhibited by structurally different OP. Oximes 68-73 acetylcholinesterase (Cartwright blood group) Homo sapiens 483-487 23047024-1 2013 Organophosphorus compounds (OPs) and oximes may interfere with other molecules than AChE in the living systems, affecting in this way various cellular processes and underlying mechanisms. Oximes 37-43 acetylcholinesterase (Cartwright blood group) Homo sapiens 84-88 23073172-1 2013 We are evaluating a facilitative transport strategy to move oximes across the blood brain barrier (BBB) to reactivate inhibited brain acetylcholinesterase (AChE). Oximes 60-66 acetylcholinesterase (Cartwright blood group) Homo sapiens 156-160 23073172-5 2013 Here we report the reactivation parameters for VX- and GB-inhibited human (Hu) AChE of the best SOx (13c) and our findings that the kinetics are similar to those of the parent oxime. Oximes 176-181 acetylcholinesterase (Cartwright blood group) Homo sapiens 79-83 22960624-4 2013 The oxime RS150D [N-((1-(3-(2-((hydroxyimino)methyl)-1H-imidazol-1-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)benzamide] was highlighted as the most promising reactivator of the tabun-hAChE conjugate. Oximes 4-9 acetylcholinesterase (Cartwright blood group) Homo sapiens 181-186 22975155-1 2013 A library of more than 200 novel uncharged oxime reactivators was used to select and refine lead reactivators of human acetylcholinesterase (hAChE) covalently conjugated with sarin, cyclosarin, VX, paraoxon and tabun. Oximes 43-48 acetylcholinesterase (Cartwright blood group) Homo sapiens 141-146 23176543-1 2013 INTRODUCTION: The more or less systematic studies on the specific activity of oximes as reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus (OP) compounds provide a panoramic image of their pharmacological and toxicological profiles. Oximes 78-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 104-124 23410111-2 2013 Although oxime nucleophiles can reactivate the AChE-phosphyl adduct, the adduct undergoes a reaction called aging. Oximes 9-14 acetylcholinesterase (Cartwright blood group) Homo sapiens 47-51 23339663-8 2013 X-ray crystallography and mass spectrometry show the formation of an aged end product formed in both AChE and BChE that cannot be reactivated by current oxime-based therapeutics. Oximes 153-158 acetylcholinesterase (Cartwright blood group) Homo sapiens 101-105 23176543-1 2013 INTRODUCTION: The more or less systematic studies on the specific activity of oximes as reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus (OP) compounds provide a panoramic image of their pharmacological and toxicological profiles. Oximes 78-84 acetylcholinesterase (Cartwright blood group) Homo sapiens 126-130 23176543-5 2013 The non-homogenous distribution of oximes versus OP in tissues was considered and correlated with the highly variable AChE reactivation at both peripheral and central levels. Oximes 35-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 118-122 22703537-11 2012 In conclusion, our work demonstrated that the newly synthesised oximes were able to reactivate not only human erythrocyte AChE but also human plasma BChE, which could represent an advantage in the treatment of OP compounds poisoning. Oximes 64-70 acetylcholinesterase (Cartwright blood group) Homo sapiens 122-126 22230262-0 2012 Comparative kinetics of organophosphates and oximes with erythrocyte, muscle and brain acetylcholinesterase. Oximes 45-51 acetylcholinesterase (Cartwright blood group) Homo sapiens 87-107 22437842-1 2012 The reactivation of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) by oximes is inadequate in case of different OP nerve agents. Oximes 92-98 acetylcholinesterase (Cartwright blood group) Homo sapiens 61-81 22437842-1 2012 The reactivation of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE) by oximes is inadequate in case of different OP nerve agents. Oximes 92-98 acetylcholinesterase (Cartwright blood group) Homo sapiens 83-87 22437842-4 2012 In part, marked differences in affinity and reactivity of the investigated oximes toward OP-inhibited human AChE were recorded. Oximes 75-81 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-112 22561105-0 2012 Kinetic interactions of a homologous series of bispyridinium monooximes (HGG oximes) with native and phosphonylated human acetylcholinesterase. Oximes 65-71 acetylcholinesterase (Cartwright blood group) Homo sapiens 122-142 22561105-1 2012 Inhibition of acetylcholinesterase (AChE) is the main toxic mechanism of organophosphorus compounds (OP) and reactivation of OP-inhibited AChE by oximes is a mainstay of antidotal treatment. Oximes 146-152 acetylcholinesterase (Cartwright blood group) Homo sapiens 36-40 22561105-1 2012 Inhibition of acetylcholinesterase (AChE) is the main toxic mechanism of organophosphorus compounds (OP) and reactivation of OP-inhibited AChE by oximes is a mainstay of antidotal treatment. Oximes 146-152 acetylcholinesterase (Cartwright blood group) Homo sapiens 138-142 22649796-2 2012 However, numerous in vitro and in vivo studies demonstrated a limited ability of these oximes to reactivate acetylcholinesterase (AChE) inhibited by different OP pesticides and nerve agents. Oximes 87-93 acetylcholinesterase (Cartwright blood group) Homo sapiens 108-128 22649796-2 2012 However, numerous in vitro and in vivo studies demonstrated a limited ability of these oximes to reactivate acetylcholinesterase (AChE) inhibited by different OP pesticides and nerve agents. Oximes 87-93 acetylcholinesterase (Cartwright blood group) Homo sapiens 130-134 22649796-3 2012 New oximes were mostly tested for their therapeutic efficacy by using different animal models and for their reactivating potency with AChE from different species. Oximes 4-10 acetylcholinesterase (Cartwright blood group) Homo sapiens 134-138 22649796-5 2012 Now, we found it tempting to determine the reactivation kinetics of a series of bispyridinium oximes bearing one or two oxime groups at different positions and having an oxybismethylene or a trimethylene linker under identical conditions with human AChE inhibited by structurally different OP. Oximes 94-99 acetylcholinesterase (Cartwright blood group) Homo sapiens 249-253 22649796-7 2012 Hence, these and previous data emphasize the necessity for thorough kinetic investigations of OP-oxime-AChE interactions and underline the difficulty to develop a broad spectrum oxime reactivator which is efficient against structurally different OP inhibitors. Oximes 97-102 acetylcholinesterase (Cartwright blood group) Homo sapiens 103-107 22343626-2 2012 Starting with the initial lead oxime RS41A identified in our earlier study and extending to the azepine analog RS194B, reactivation rates for OP-hAChE conjugates formed by sarin, cyclosarin, VX, paraoxon, and tabun are enhanced severalfold in vitro. Oximes 31-36 acetylcholinesterase (Cartwright blood group) Homo sapiens 145-150 22230262-1 2012 There is an ongoing debate whether oximes can effectively counteract the effects of organophosphorus compounds (OP) on brain acetylcholinesterase (AChE) activity and whether there are differences in the kinetic properties of brain and erythrocyte AChE. Oximes 35-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 125-145 22230262-1 2012 There is an ongoing debate whether oximes can effectively counteract the effects of organophosphorus compounds (OP) on brain acetylcholinesterase (AChE) activity and whether there are differences in the kinetic properties of brain and erythrocyte AChE. Oximes 35-41 acetylcholinesterase (Cartwright blood group) Homo sapiens 147-151 22230262-7 2012 These data support the view that AChE from different tissue has similar kinetic properties and that brain AChE is comparably susceptible toward reactivation by oximes. Oximes 160-166 acetylcholinesterase (Cartwright blood group) Homo sapiens 106-110 21998030-2 2012 Being the key target of OP toxicity, AChE may serve as a valuable tool for diagnosis of OP exposure as well as for the investigation of the kinetics of interactions between OP and oximes. Oximes 180-186 acetylcholinesterase (Cartwright blood group) Homo sapiens 37-41 22447833-1 2012 Oxime HI-6 is an efficient reactivator of the acetylcholinesterase inhibited by organophosphorous nerve agents. Oximes 0-5 acetylcholinesterase (Cartwright blood group) Homo sapiens 46-66 22309910-1 2012 We earlier reported an in silico pharmacophore model for reactivation of oximes to tabun-inhibited AChE. Oximes 73-79 acetylcholinesterase (Cartwright blood group) Homo sapiens 99-103 22309910-2 2012 Since DFP (diisopropylfluorophosphate) like tabun is a G-agent simulator, we utilized the model as a rational strategy to discover non-oxime reactivators of DFP-inhibited AChE in this study. Oximes 135-140 acetylcholinesterase (Cartwright blood group) Homo sapiens 171-175 22309910-4 2012 The procedure led us to identify several potent non-oxime compounds that reactivate DFP-inhibited AChE. Oximes 52-57 acetylcholinesterase (Cartwright blood group) Homo sapiens 98-102