PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 14672944-3 2004 Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. Diphosphonates 52-66 farnesyl diphosphate synthase Homo sapiens 80-84 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 122-153 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 155-159 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 226-240 farnesyl diphosphate synthase Homo sapiens 122-153 16892359-1 2006 To understand the structural basis for bisphosphonate therapy of bone diseases, we solved the crystal structures of human farnesyl pyrophosphate synthase (FPPS) in its unliganded state, in complex with the nitrogen-containing bisphosphonate (N-BP) drugs zoledronate, pamidronate, alendronate, and ibandronate, and in the ternary complex with zoledronate and the substrate isopentenyl pyrophosphate (IPP). Diphosphonates 226-240 farnesyl diphosphate synthase Homo sapiens 155-159 15828834-1 2005 We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. Diphosphonates 65-80 farnesyl diphosphate synthase Homo sapiens 235-264 15828834-1 2005 We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. Diphosphonates 65-80 farnesyl diphosphate synthase Homo sapiens 266-270 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 19-34 farnesyl diphosphate synthase Homo sapiens 38-69 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 19-34 farnesyl diphosphate synthase Homo sapiens 71-75 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 170-173 farnesyl diphosphate synthase Homo sapiens 38-69 16831938-10 2006 The key target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS) within osteoclasts, and the recently elucidated crystal structure of this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 170-173 farnesyl diphosphate synthase Homo sapiens 71-75 16932286-2 2006 When embedded in bone matrix, bisphosphonates are taken up by osteoclasts engaged in bone resorption, leading--mainly by inhibition of farnesyl diphosphate synthase, a key enzyme of the mevalonate pathway--to osteoclast apoptosis. Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 135-164 16216433-4 2006 Recently, farnesyl pyrophosphate synthase has been shown as a molecular target of nitrogen-containing bisphosphonates, and inhibition of post-translational prenylation of small molecular weight G proteins is likely involved in their anti-resorptive activity on osteoclasts. Diphosphonates 102-117 farnesyl diphosphate synthase Homo sapiens 10-41 11160603-2 2001 Recently, several nitrogen-containing bisphosphonates were found to inhibit osteoclast-mediated bone resorption in vitro by inhibiting farnesyl diphosphate synthase, thereby preventing protein prenylation in osteoclasts. Diphosphonates 38-53 farnesyl diphosphate synthase Homo sapiens 135-164 14711309-7 2004 Since bisphosphonates are known to be potent, nanomolar inhibitors of the mevalonate/isoprene pathway enzyme farnesyl pyrophosphate synthase (FPPS), we also compared the pharmacophores for gammadelta T cell activation with those for FPPS inhibition, using the Catalyst program. Diphosphonates 6-21 farnesyl diphosphate synthase Homo sapiens 109-140 14711309-7 2004 Since bisphosphonates are known to be potent, nanomolar inhibitors of the mevalonate/isoprene pathway enzyme farnesyl pyrophosphate synthase (FPPS), we also compared the pharmacophores for gammadelta T cell activation with those for FPPS inhibition, using the Catalyst program. Diphosphonates 6-21 farnesyl diphosphate synthase Homo sapiens 142-146 14711309-9 2004 In addition, the CoMSIA fields were quite similar to those found for FPPS inhibition by bisphosphonates. Diphosphonates 88-103 farnesyl diphosphate synthase Homo sapiens 69-73 14711309-10 2004 The activities of the bisphosphonates in gammadelta T cell activation were highly correlated with their activities in FPPS inhibition: R = 0.88, p = 0.002, versus a human recombinant FPPS (N = 9 compounds); R = 0.82, p < 0.0001, for an expressed Leishmania major FPPS (N = 45 compounds). Diphosphonates 22-37 farnesyl diphosphate synthase Homo sapiens 118-122 16036064-5 2003 For nitrogen-containing bisphosphonates, the direct intracellular target is the enzyme farnesyl diphosphate synthase in the cholesterol biosynthetic pathway. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 87-116 12177810-4 2002 Nitrogen-containing bisphosphonates were shown to inhibit farnesyl diphosphate synthase, thus blocking the synthesis of higher isoprenoids. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 58-87 11785983-0 2002 Identification of a bisphosphonate that inhibits isopentenyl diphosphate isomerase and farnesyl diphosphate synthase. Diphosphonates 20-34 farnesyl diphosphate synthase Homo sapiens 87-116 11785983-1 2002 We and others have recently shown that the major molecular target of nitrogen-containing bisphosphonate drugs is farnesyl diphosphate synthase, an enzyme in the mevalonate pathway. Diphosphonates 89-103 farnesyl diphosphate synthase Homo sapiens 113-142 11785983-2 2002 In an in vitro screen, we discovered a bisphosphonate, NE21650, that potently inhibited farnesyl diphosphate synthase but, unlike other N-BPs investigated, was also a weak inhibitor of isopentenyl diphosphate isomerase. Diphosphonates 39-53 farnesyl diphosphate synthase Homo sapiens 88-117 11785983-4 2002 Our observations show that minor changes to the structure of bisphosphonates allow inhibition of more than one enzyme in the mevalonate pathway and suggest that loss of protein prenylation due to inhibition of more than one enzyme in the mevalonate pathway may lead to an increase in antiresorptive potency compared to bisphosphonates that only inhibit farnesyl diphosphate synthase. Diphosphonates 61-76 farnesyl diphosphate synthase Homo sapiens 353-382 11160603-6 2001 Furthermore, minor changes to the structure of the R(2) side chain of heterocycle-containing bisphosphonates, giving rise to less potent inhibitors of bone resorption in vivo, also caused a reduction in potency up to approximately 300-fold for inhibition of farnesyl diphosphate synthase in vitro. Diphosphonates 93-108 farnesyl diphosphate synthase Homo sapiens 258-287 14529538-5 2003 By contrast, the more potent, nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Diphosphonates 50-65 farnesyl diphosphate synthase Homo sapiens 223-235 14529538-8 2003 Identification of FPP synthase as the target of nitrogen-containing bisphosphonates has also helped explain the molecular basis for the adverse effects of these agents in the GI tract and on the immune system. Diphosphonates 68-83 farnesyl diphosphate synthase Homo sapiens 18-30 35456610-7 2022 Several SNPs located in genes FDPS and FNTA were associated with the bisphosphonate-induced changes in hip bone mineral density (BMD), whereas polymorphisms of the PDSS1, CYP19A1, CYP1A1, and CYP1A2 genes were associated with SERM-induced changes in spine BMD. Diphosphonates 69-83 farnesyl diphosphate synthase Homo sapiens 30-34 10620343-9 2000 These findings (i) identify farnesyl diphosphate synthase as the selective target of alendronate in the mevalonate pathway, (ii) show that this enzyme is inhibited by other N-containing bisphosphonates, such as risendronate, but not by clodronate, supporting a different mechanism of action for different bisphosphonates, and (iii) document in purified osteoclasts alendronate inhibition of prenylation and sterol biosynthesis. Diphosphonates 186-201 farnesyl diphosphate synthase Homo sapiens 28-57 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 283-312 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 314-318 34896359-7 2022 The synthesis and biological evaluation of a large number of nitrogen-containing bisphosphonates in the 1980s and 1990s led to the key discovery that the antiresorptive effects of these more complex analogs on osteoclasts result mostly from their potency as inhibitors of the enzyme farnesyl diphosphate synthase (FDPS/FPPS). Diphosphonates 81-96 farnesyl diphosphate synthase Homo sapiens 319-323 34896359-9 2022 Since then, it has become even more clear that the overall pharmacological effects of individual bisphosphonates on bone depend upon two key properties: the affinity for bone mineral and inhibitory effects on biochemical targets within bone cells, in particular FDPS. Diphosphonates 97-112 farnesyl diphosphate synthase Homo sapiens 262-266 35600875-3 2022 Nitrogen-containing bisphosphonates suppress osteoclastic resorption by inhibiting farnesyl pyrophosphate synthase in the mevalonate pathway, leading to deficiency of the substrate for GTPase prenylation. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 83-114 10049736-0 1999 Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 80-111 21702715-7 2011 Remarkable for their high bone mineral affinity, BPs are structural mimics of the dimethylallyl pyrophosphate substrate of FPPS, and constitute the major type of FPPS inhibitor currently used in the clinic for treatment of bone-related diseases. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 123-127 21702715-7 2011 Remarkable for their high bone mineral affinity, BPs are structural mimics of the dimethylallyl pyrophosphate substrate of FPPS, and constitute the major type of FPPS inhibitor currently used in the clinic for treatment of bone-related diseases. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 162-166 35456610-8 2022 After multivariate analyses, genotypes combining genes FDPS and FNTA showed a stronger association with bisphosphonate response (r = 0.34; p = 0.00009), whereas the combination of CYP19A1 and PDSS1 genotypes was associated with the response to SERMs (r = 0.62, p = 0.0003). Diphosphonates 104-118 farnesyl diphosphate synthase Homo sapiens 55-59 33559705-2 2021 Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. Diphosphonates 10-25 farnesyl diphosphate synthase Homo sapiens 240-269 33559705-2 2021 Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. Diphosphonates 41-56 farnesyl diphosphate synthase Homo sapiens 240-269 32537808-2 2020 Nitrogen-containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the T. brucei parasites by inhibiting farnesyl pyrophosphate synthase (FPPS); however, due to their poor pharmacokinetic properties they are not well suited for anti-parasitic therapy. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 186-190 31699606-3 2019 The lead carboxyphosphonate inhibits geranylgeranyl transferase II while its corresponding bisphosphonate analogue potently inhibits farnesyl diphosphate synthase. Diphosphonates 91-105 farnesyl diphosphate synthase Homo sapiens 133-162 31785819-0 2020 Structure-based virtual screening and biological evaluation of novel non-bisphosphonate farnesyl pyrophosphate synthase inhibitors. Diphosphonates 73-87 farnesyl diphosphate synthase Homo sapiens 88-119 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 0-31 32057422-1 2020 Farnesyl pyrophosphate synthase (FPPS) is a crucial enzyme for the synthesis of isoprenoids and the key target of nitrogen-containing bisphosphonates (N-BPs). Diphosphonates 134-149 farnesyl diphosphate synthase Homo sapiens 0-31 32057422-1 2020 Farnesyl pyrophosphate synthase (FPPS) is a crucial enzyme for the synthesis of isoprenoids and the key target of nitrogen-containing bisphosphonates (N-BPs). Diphosphonates 134-149 farnesyl diphosphate synthase Homo sapiens 33-37 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 33-37 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 122-137 farnesyl diphosphate synthase Homo sapiens 158-162 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 0-31 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 33-37 31785819-1 2020 Farnesyl pyrophosphate synthase (FPPS) is known to participate in a variety of disease-related cell signaling pathway and bisphosphonates (BPs) are served as FPPS inhibitors. Diphosphonates 139-142 farnesyl diphosphate synthase Homo sapiens 158-162 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 183-214 31023104-2 2019 The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Diphosphonates 24-27 farnesyl diphosphate synthase Homo sapiens 114-143 31023104-2 2019 The nitrogen-containing BPs (NBPs) target osteoclast activity by disrupting protein prenylation via inhibition of farnesyl diphosphate synthase (FDPS). Diphosphonates 24-27 farnesyl diphosphate synthase Homo sapiens 145-149 30036888-0 2019 QSAR Models for Nitrogen Containing Monophosphonate and Bisphosphonate Derivatives as Human Farnesyl Pyrophosphate Synthase Inhibitors Based on Monte Carlo Method. Diphosphonates 56-70 farnesyl diphosphate synthase Homo sapiens 92-123 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 223-227 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 183-214 30096489-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 223-227 26457482-3 2015 However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 156-187 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 183-214 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 223-227 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 183-214 32002964-4 2018 Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. Diphosphonates 17-20 farnesyl diphosphate synthase Homo sapiens 223-227 29080272-1 2018 Nitrogen-containing bisphosphonates (N-BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 126-157 29080272-1 2018 Nitrogen-containing bisphosphonates (N-BPs) have been used widely to treat various bone diseases by inhibiting the key enzyme farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 159-163 29276048-3 2018 Unfortunately, current bisphosphonate drugs that inhibit FPPS and GGPPS enzymes by acting as a diphosphate substrate analog show poor bioavailability and selectivity for PfFPPS/GGPPS. Diphosphonates 23-37 farnesyl diphosphate synthase Homo sapiens 57-61 29276048-4 2018 We identified a new non-bisphosphonate compound, MMV019313, which is highly selective for PfFPPS/GGPPS and showed no activity against human FPPS or GGPPS. Diphosphonates 24-38 farnesyl diphosphate synthase Homo sapiens 92-96 29683099-7 2018 Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 48-77 28559264-3 2017 The target of the most potent bisphosphonates is the isoprenoid biosynthesis pathway enzyme farnesyl diphosphate synthase (FPPS). Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 123-127 28631130-0 2017 New insights into human farnesyl pyrophosphate synthase inhibition by second-generation bisphosphonate drugs. Diphosphonates 88-102 farnesyl diphosphate synthase Homo sapiens 24-55 26781029-7 2016 EXPERT OPINION: Notwithstanding their lack of drug-like character, bisphosphonates are still the most advantageous class of inhibitors of the enzymatic activity of farnesyl pyrophosphate synthase. Diphosphonates 67-82 farnesyl diphosphate synthase Homo sapiens 164-195 26891809-5 2016 Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. Diphosphonates 145-160 farnesyl diphosphate synthase Homo sapiens 85-114 26891809-5 2016 Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. Diphosphonates 145-160 farnesyl diphosphate synthase Homo sapiens 116-120 28723699-18 2018 The correlation found with the intake of bisphosphonates, capable of inhibiting the action of the farnesyl pyrophosphate synthase enzyme, thus influencing coagulation, requires further prospective studies with research of the methylene tetrahydrofolate reductase mutation in patients with OI type III undergoing surgical procedures. Diphosphonates 41-56 farnesyl diphosphate synthase Homo sapiens 98-129 27428767-5 2016 This fluorescence probe was used to reveal the inhibitory mechanism of zoledronate, a bisphosphonate drug that targets human FPPS and possibly GGPPS. Diphosphonates 86-100 farnesyl diphosphate synthase Homo sapiens 125-129 26457482-3 2015 However, bisphosphonate bone affinity is often considered too strong and cannot be significantly modulated without losing activity on the enzymatic target, farnesyl pyrophosphate synthase (FPPS). Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 189-193 25130632-6 2014 Moreover, polymorphisms of CYP2C gene, but also FDPS may identify patients with high risk of undesirable effects of bisphosphonates (osteonecrosis of jaw). Diphosphonates 116-131 farnesyl diphosphate synthase Homo sapiens 48-52 26381451-2 2015 Currently available anti-FPPS drugs are active-site-directed bisphosphonate inhibitors, the peculiar pharmacological profile of which is inadequate for therapeutic indications beyond bone diseases. Diphosphonates 61-75 farnesyl diphosphate synthase Homo sapiens 25-29 26381451-0 2015 Discovery of Novel Allosteric Non-Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthase by Integrated Lead Finding. Diphosphonates 34-48 farnesyl diphosphate synthase Homo sapiens 63-94 25630225-1 2015 In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. Diphosphonates 40-54 farnesyl diphosphate synthase Homo sapiens 122-153 25630225-1 2015 In order to explore the interactions of bisphosphonate ligands with the active site and an allosteric pocket of the human farnesyl pyrophosphate synthase (hFPPS), substituted indole and azabenzimidazole bisphosphonates were designed as chameleon ligands. Diphosphonates 40-54 farnesyl diphosphate synthase Homo sapiens 155-160 26381451-3 2015 The recent discovery of an allosteric binding site has paved the way toward the development of novel non-bisphosphonate FPPS inhibitors with broader therapeutic potential, notably as immunomodulators in oncology. Diphosphonates 105-119 farnesyl diphosphate synthase Homo sapiens 120-124 26314394-0 2015 Protonation State and Hydration of Bisphosphonate Bound to Farnesyl Pyrophosphate Synthase. Diphosphonates 35-49 farnesyl diphosphate synthase Homo sapiens 59-90 25815158-4 2015 With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. Diphosphonates 9-23 farnesyl diphosphate synthase Homo sapiens 78-82 25815158-4 2015 With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. Diphosphonates 178-192 farnesyl diphosphate synthase Homo sapiens 78-82 24911527-1 2014 Human farnesyl pyrophosphate synthase (hFPPS) is the gate-keeper of mammalian isoprenoids and the key target of bisphosphonate drugs. Diphosphonates 112-126 farnesyl diphosphate synthase Homo sapiens 6-37 24911527-1 2014 Human farnesyl pyrophosphate synthase (hFPPS) is the gate-keeper of mammalian isoprenoids and the key target of bisphosphonate drugs. Diphosphonates 112-126 farnesyl diphosphate synthase Homo sapiens 39-44 24699741-1 2014 Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 178-209 24369118-0 2014 Upregulation of endogenous farnesyl diphosphate synthase overcomes the inhibitory effect of bisphosphonate on protein prenylation in Hela cells. Diphosphonates 92-106 farnesyl diphosphate synthase Homo sapiens 27-56 24699741-1 2014 Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 211-215 24598749-4 2014 Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 A are reported. Diphosphonates 147-162 farnesyl diphosphate synthase Homo sapiens 60-64 24598749-8 2014 Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. Diphosphonates 113-128 farnesyl diphosphate synthase Homo sapiens 41-45 24598749-8 2014 Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. Diphosphonates 113-128 farnesyl diphosphate synthase Homo sapiens 49-53 24598914-3 2014 Crystal structures of hFPPS in ternary complexes with a novel bisphosphonate, YS0470, and the secondary ligands inorganic phosphate (Pi), inorganic pyrophosphate (PPi) and isopentenyl pyrophosphate (IPP) have recently been reported. Diphosphonates 62-76 farnesyl diphosphate synthase Homo sapiens 22-27 24246954-0 2014 Syntheses and characterization of non-bisphosphonate quinoline derivatives as new FPPS inhibitors. Diphosphonates 38-52 farnesyl diphosphate synthase Homo sapiens 82-86 24246954-11 2014 GENERAL SIGNIFICANCE: The traditional FPPS active-site inhibitors bisphosphonates show poor membrane permeability to tumor cells, due to their strong polarity. Diphosphonates 66-81 farnesyl diphosphate synthase Homo sapiens 38-42 24172032-0 2014 Thermodynamic evaluation of the binding of bisphosphonates to human farnesyl pyrophosphate synthase. Diphosphonates 43-58 farnesyl diphosphate synthase Homo sapiens 68-99 24172032-2 2014 BPs with nitrogen-containing side chains (N-BPs) are known to act as inhibitors for farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. Diphosphonates 0-3 farnesyl diphosphate synthase Homo sapiens 84-115 24172032-2 2014 BPs with nitrogen-containing side chains (N-BPs) are known to act as inhibitors for farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway. Diphosphonates 0-3 farnesyl diphosphate synthase Homo sapiens 117-121 24172032-3 2014 In this study, we evaluated the effect of different side chains on the binding affinity of BPs to human FPPS using calorimetric techniques. Diphosphonates 91-94 farnesyl diphosphate synthase Homo sapiens 104-108 24172032-4 2014 Differential scanning calorimetry (DSC) was used to determine the thermal unfolding of FPPS in the presence of BPs. Diphosphonates 111-114 farnesyl diphosphate synthase Homo sapiens 87-91 24172032-5 2014 The addition of a series of clinically available BPs increased the structural stability of human FPPS by preferential binding, as indicated by an increase in the FPPS unfolding temperature. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 97-101 24172032-5 2014 The addition of a series of clinically available BPs increased the structural stability of human FPPS by preferential binding, as indicated by an increase in the FPPS unfolding temperature. Diphosphonates 49-52 farnesyl diphosphate synthase Homo sapiens 162-166 24172032-6 2014 The magnitude of the increase was correlated with in vivo antiresorptive efficacy, suggesting that the stabilization of FPPS underlies the inhibitory effect of the BPs. Diphosphonates 164-167 farnesyl diphosphate synthase Homo sapiens 120-124 24172032-7 2014 Isothermal titration calorimetry (ITC) experiments were performed to evaluate the binding thermodynamics of BPs against human FPPS. Diphosphonates 108-111 farnesyl diphosphate synthase Homo sapiens 126-130 22842101-4 2013 Recent studies have validated FPPS as a molecular target of bisphosphonates for drug development against tumors as well as human pathogens. Diphosphonates 60-75 farnesyl diphosphate synthase Homo sapiens 30-34 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 41-72 23919676-1 2013 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS). Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 74-78 23794630-1 2013 The potent nitrogen-containing bisphosphonate zoledronate inhibits farnesyl pyrophosphate synthase, a key enzyme of the mevalonate pathway that is often hyperactive in malignant cells. Diphosphonates 31-45 farnesyl diphosphate synthase Homo sapiens 67-98 23610597-1 2013 We synthesized 30 lipophilic bisphosphonates and tested them in malaria parasite killing (targeting parasite geranylgeranyl diphosphate synthase, GGPPS) as well in human gammadelta T cell activation (targeting human farnesyl diphosphate synthase, FPPS). Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 247-251 25365870-1 2014 Bisphosphonates are chemical analogs of isoprene lipids, which competitively decrease the activity of farnesyl diphosphate synthase in osteoclasts and thus retard prenylation. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 102-131 23421555-2 2013 Here, we used this approach combined with similarity searches and experimental inhibition assays to identify several low micromolar, non-bisphosphonate inhibitors, bisamidines, of farnesyl diphosphate synthase (FPPS), an enzyme targeted by some anticancer and antimicrobial agents and for the treatment of bone resorption diseases. Diphosphonates 137-151 farnesyl diphosphate synthase Homo sapiens 180-209 23421555-3 2013 This novel class of farnesyl diphosphate synthase inhibitors have more drug-like properties than existing bisphosphonate inhibitors, making them interesting pharmaceutical leads. Diphosphonates 106-120 farnesyl diphosphate synthase Homo sapiens 20-49 23234314-2 2012 Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 35-39 23533771-4 2013 In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 37-40 farnesyl diphosphate synthase Homo sapiens 91-126 23533771-4 2013 In addition, the nitrogen-containing BPs (N-BPs), second-generation BPs, act by inhibiting farnesyl diphosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 44-47 farnesyl diphosphate synthase Homo sapiens 91-126 23234314-3 2012 Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme"s C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP). Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 20-24 23234314-5 2012 The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation. Diphosphonates 60-74 farnesyl diphosphate synthase Homo sapiens 31-35 22884353-0 2012 Design of potent bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase via targeted interactions with the active site "capping" phenyls. Diphosphonates 17-31 farnesyl diphosphate synthase Homo sapiens 56-87 22884353-1 2012 Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 91-122 22884353-1 2012 Nitrogen-containing bisphosphonates (N-BPs) are potent active site inhibitors of the human farnesyl pyrophosphate synthase (hFPPS) and valuable human therapeutics for the treatment of bone-related malignancies. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 124-129 21864230-11 2012 The more potent nitrogen-containing BPs inhibit FPPS, a key enzyme in the mevalonate pathway. Diphosphonates 36-39 farnesyl diphosphate synthase Homo sapiens 48-52 21151198-0 2012 Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates. Diphosphonates 114-129 farnesyl diphosphate synthase Homo sapiens 31-60 21111853-4 2011 The considerably more potent nitrogen-containing bisphosphonates are not metabolised but potently inhibit farnesyl pyrophosphate (FPP) synthase, a key enzyme of the mevalonate pathway. Diphosphonates 49-64 farnesyl diphosphate synthase Homo sapiens 106-143 22091898-6 2011 Second-generation bisphosphonates are nitrogen-containing agents; these inhibit osteoclast vesicular trafficking, membrane ruffling, morphology, and cytoskeletal arrangement by inhibiting farnesyl diphosphate synthase in the mevalonate pathway. Diphosphonates 18-33 farnesyl diphosphate synthase Homo sapiens 188-217 21111853-8 2011 These discoveries are also giving insights into some of the adverse effects of bisphosphonates, such as the acute phase reaction that is triggered by inhibition of FPP synthase in peripheral blood monocytes. Diphosphonates 79-94 farnesyl diphosphate synthase Homo sapiens 164-176 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 47-78 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 80-84 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 152-155 farnesyl diphosphate synthase Homo sapiens 47-78 21555003-14 2011 The major enzyme target for bisphosphonates is farnesyl pyrophosphate synthase (FPPS), and the crystal structure elucidated for this enzyme reveals how BPs bind to and inhibit at the active site via their critical N atoms. Diphosphonates 152-155 farnesyl diphosphate synthase Homo sapiens 80-84 21497677-7 2011 A major advance was the discovery that the anti-resorptive effects of the nitrogen-containing bisphosphonates (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their potency as inhibitors of the enzyme farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 94-109 farnesyl diphosphate synthase Homo sapiens 256-287 21497677-7 2011 A major advance was the discovery that the anti-resorptive effects of the nitrogen-containing bisphosphonates (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their potency as inhibitors of the enzyme farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 94-109 farnesyl diphosphate synthase Homo sapiens 289-293 21465521-6 2011 Further studies show that bisphosphonates inhibit farnesyl pyrophosphate synthase, a critical enzyme required for synthesis of isoprenyl and geranylgeranyl, and inhibit prenylation and geranylgeranylation of small G-proteins such as Rac and Rho. Diphosphonates 26-41 farnesyl diphosphate synthase Homo sapiens 50-81 21335425-3 2011 We hypothesized that inhibition of farnesyl diphosphate synthase (FDPS) and geranylgeranyl diphosphate synthase (GGDPS) by bisphosphonates would induce autophagy by depleting cellular geranylgeranyl diphosphate (GGPP) and impairing protein geranylgeranylation. Diphosphonates 123-138 farnesyl diphosphate synthase Homo sapiens 35-64 21335425-3 2011 We hypothesized that inhibition of farnesyl diphosphate synthase (FDPS) and geranylgeranyl diphosphate synthase (GGDPS) by bisphosphonates would induce autophagy by depleting cellular geranylgeranyl diphosphate (GGPP) and impairing protein geranylgeranylation. Diphosphonates 123-138 farnesyl diphosphate synthase Homo sapiens 66-70 21247791-3 2011 Nitrogen-containing bisphosphonates (N-BPs) are particularly able to inhibit pyrophosphate synthase (FPPS) in the mevalonate pathway (MVP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 101-105 21237288-6 2011 The nitrogen-containing bisphosphonates pamidronate and zoledronate specifically inhibit farnesyl pyrophosphate synthase indicated by the accumulation of IPP/DMAPP. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 89-120 21145999-4 2011 The nitrogen-containing bisphosphonates, such as alendronate, act as inhibitors of farnesyl-pyrophosphate synthase, which leads to inhibition of the prenylation of many intracellular signaling proteins. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 83-114 21420384-1 2011 A class of drugs successfully used for treatment of metabolic bone diseases is the nitrogen-containing bisphosphonates (N-BPs), which act by inhibiting the vital enzyme, farnesyl pyrophosphate synthase (FPPS), of the mevalonate pathway. Diphosphonates 103-118 farnesyl diphosphate synthase Homo sapiens 170-201 21420384-1 2011 A class of drugs successfully used for treatment of metabolic bone diseases is the nitrogen-containing bisphosphonates (N-BPs), which act by inhibiting the vital enzyme, farnesyl pyrophosphate synthase (FPPS), of the mevalonate pathway. Diphosphonates 103-118 farnesyl diphosphate synthase Homo sapiens 203-207 20533067-5 2010 Compared with other BPs, zoledronic acid (ZOL) has a higher affinity to bone mineral and is a stronger inhibitor of the enzyme farnesyl pyrophosphate synthase (the main target of nitrogen-containing BPs), properties that explain the prolonged effect of ZOL on bone turnover and render it a therapeutic option for JPD, similar to PDB. Diphosphonates 199-202 farnesyl diphosphate synthase Homo sapiens 127-158 21110804-6 2011 First, we summarize the interactions between ligands and proteins observed in N-BPs-FPPS complexes in the Protein Data Bank (PDB). Diphosphonates 80-83 farnesyl diphosphate synthase Homo sapiens 84-88 21196316-4 2011 To determine if a higher sensitivity to bisphosphonates could in part explain the development of ONJ, the segregation of A/C rs2297480 polymorphism of gene encoding for the farnesyl pyrophosphate synthase (FDPS) with ONJ was evaluated in a cohort of 68 Caucasian patients treated with zoledronic acid for multiple myeloma and metastatic mammary and prostate cancer. Diphosphonates 40-55 farnesyl diphosphate synthase Homo sapiens 173-204 20801032-0 2010 Novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase. Diphosphonates 6-20 farnesyl diphosphate synthase Homo sapiens 45-76 20832326-2 2010 For example, the nitrogenous bisphosphonates zoledronate and risedronate inhibit the enzyme farnesyl diphosphate synthase while digeranyl bisphosphonate has been shown to inhibit the enzyme geranylgeranyl diphosphate synthase. Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 92-121 20801032-1 2010 A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Diphosphonates 58-72 farnesyl diphosphate synthase Homo sapiens 97-128 20801032-1 2010 A structure-based approach was pursued in designing novel bisphosphonate inhibitors of the human farnesyl pyrophosphate synthase (hFPPS). Diphosphonates 58-72 farnesyl diphosphate synthase Homo sapiens 130-135 20544107-2 2010 We synthesized and studied a new type of nitrogen-containing bisphosphonate analogs and developed a sensitive end point assay method for enzyme FPPS, which was used for inhibitor screening. Diphosphonates 61-75 farnesyl diphosphate synthase Homo sapiens 144-148 20711197-1 2010 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget"s disease and tumor-induced osteolysis. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 41-72 20711197-1 2010 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget"s disease and tumor-induced osteolysis. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 74-78 20544107-3 2010 One potent FPPS inhibitor was discovered, and the structure-activity relationship of bisphosphonates for the enzyme inactivation was studied. Diphosphonates 85-100 farnesyl diphosphate synthase Homo sapiens 11-15 20539033-3 2010 At the molecular level, bisphosphonates exert their anti-resorptive effects by inhibiting farnesyl pyrophosphate synthase activity within osteoclasts. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 90-121 20450493-2 2010 FDPS is also the molecular target of nitrogen-containing bisphosphonates, which are used as bone-antiresorptive drugs in various disorders. Diphosphonates 57-72 farnesyl diphosphate synthase Homo sapiens 0-4 20299227-5 2010 Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. Diphosphonates 32-47 farnesyl diphosphate synthase Homo sapiens 61-92 19819230-3 2010 FPPS inhibition leads also to the accumulation of isopentenyl pyrophosphate (IPP) and the apoptotic ATP analog, ApppI, but the role of this mechanism in the cytotoxic action of bisphosphonates is less clear. Diphosphonates 177-192 farnesyl diphosphate synthase Homo sapiens 0-4 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 farnesyl diphosphate synthase Homo sapiens 89-118 20722616-3 2010 The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. Diphosphonates 11-26 farnesyl diphosphate synthase Homo sapiens 216-228 20722616-3 2010 The simple bisphosphonates, clodronate, etidronate and tiludronate, are intracellularly metabolised to cytotoxic ATP analogues, while the more potent, nitrogen-containing bisphosphonates act by inhibiting the enzyme FPP synthase, thereby preventing the prenylation of small GTPases that are necessary for the normal function and survival of osteoclasts. Diphosphonates 171-186 farnesyl diphosphate synthase Homo sapiens 216-228 19699819-4 2009 Nitrogen-containing bisphosphonates (N-BPs), including zoledronic acid (ZOL), act by inhibiting farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 96-127 19699819-4 2009 Nitrogen-containing bisphosphonates (N-BPs), including zoledronic acid (ZOL), act by inhibiting farnesyl pyrophosphate synthase (FPPS). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 129-133 19665949-1 2009 Nitrogen-containing bisphosphonates (N-BPs) are shown to inhibit a key enzyme of intracellular mevalonate pathway, FPP synthase, leading to intracellular accumulation of pathway metabolites isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 115-127 19810397-5 2009 The potency of the various nitrogen-containing bisphosphonates is dependent on a number of factors including bone binding, zeta potential and inhibition of the enzyme farnesyl pyrophosphate synthase. Diphosphonates 47-62 farnesyl diphosphate synthase Homo sapiens 167-198 20191015-2 2010 The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. Diphosphonates 210-224 farnesyl diphosphate synthase Homo sapiens 84-113 20191015-2 2010 The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. Diphosphonates 210-224 farnesyl diphosphate synthase Homo sapiens 115-119 19233551-2 2009 Nitrogen-containing bisphosphonates (N-BPs) are inhibitors of farnesyl diphosphate (FPP) synthase as well as chelators of divalent cations. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 62-97 19371349-2 2009 Nitrogen-containing bisphosphonates (N-BPs), such as zoledronic acid, induce the formation of a novel ATP analogue (1-adenosin-5"-yl ester 3-(3-methylbut-3-enyl) ester triphosphoric acid; ApppI), as a consequence of the inhibition of farnesyl pyrophosphate synthase and the accumulation of isopentenyl pyrophosphate (IPP). Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 234-265 19309137-2 2009 Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Diphosphonates 235-250 farnesyl diphosphate synthase Homo sapiens 120-124 19016713-1 2009 Nitrogen-containing bisphosphonates indirectly activate Vgamma9Vdelta2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vgamma9Vdelta2 T cell activation through IPP/DMAPP accumulation are unknown. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 101-132 18327899-0 2008 Structure-activity relationships among the nitrogen containing bisphosphonates in clinical use and other analogues: time-dependent inhibition of human farnesyl pyrophosphate synthase. Diphosphonates 63-78 farnesyl diphosphate synthase Homo sapiens 151-182 18800762-2 2008 Bisphosphonates containing unbranched side chains bind to either the farnesyl diphosphate (FPP) substrate site, the geranylgeranyl diphosphate (GGPP) product site, and in one case, both sites, with the bisphosphonate moiety interacting with 3 Mg (2+) that occupy the same position as found in FPP synthase. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 293-305 18463892-8 2008 This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Diphosphonates 108-122 farnesyl diphosphate synthase Homo sapiens 143-174 18214569-7 2008 The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. Diphosphonates 54-57 farnesyl diphosphate synthase Homo sapiens 178-209 18214569-7 2008 The antiresorptive effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) appear to result from their inhibition of the enzyme farnesyl pyrophosphate synthase (FPPS) in osteoclasts. Diphosphonates 54-57 farnesyl diphosphate synthase Homo sapiens 211-215 18442135-1 2008 We report the X-ray crystallographic structures of the bisphosphonate N-[methyl(4-phenylbutyl)]-3-aminopropyl-1-hydroxy-1,1-bisphosphonate (BPH-210), a potent analog of pamidronate (Aredia), bound to farnesyl diphosphate synthase (FPPS) from Trypanosoma brucei as well as to geranylgeranyl diphosphate synthase from Saccharomyces cerevisiae. Diphosphonates 55-69 farnesyl diphosphate synthase Homo sapiens 231-235 18442135-6 2008 In this case, the bisphosphonate binds only to the GGPP product inhibitory site, with only 1 (chain A) or 0 (chain B) Mg(2+), and DeltaS is much smaller and DeltaH is approximately 6 k cal more negative than in the case of FPPS binding. Diphosphonates 18-32 farnesyl diphosphate synthase Homo sapiens 223-227 16996129-2 2007 Newer nitrogen containing bisphosphonates such as zoledronate act, at least in part, by inhibiting farnesyl diphosphate synthase and subsequent protein prenylation, furthermore, limited data suggests that zoledronate exerts a direct anti-tumour effect against human myeloma cell lines. Diphosphonates 26-41 farnesyl diphosphate synthase Homo sapiens 99-128 18454049-8 2008 The production of cytotoxic ATP analogs in tumor cells after BP treatment is likely to depend on the activity of enzymes, such as farnesyl diphosphate synthase or aminoacyl-tRNA synthetases, responsible for ATP analog formation. Diphosphonates 61-63 farnesyl diphosphate synthase Homo sapiens 130-159 17535895-1 2007 Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 91-120 17535895-1 2007 Bisphosphonate drugs (e.g., Fosamax and Zometa) are thought to act primarily by inhibiting farnesyl diphosphate synthase (FPPS), resulting in decreased prenylation of small GTPases. Diphosphonates 0-14 farnesyl diphosphate synthase Homo sapiens 122-126 18473904-2 2008 Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 58-62 18473904-2 2008 Antiprotozoal properties of bisphosphonates, which target FPPS, have generated interest in FPPS as a potential antiprotozoal drug target. Diphosphonates 28-43 farnesyl diphosphate synthase Homo sapiens 91-95 18056045-5 2007 The inhibitory effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 50-53 farnesyl diphosphate synthase Homo sapiens 178-209 18056045-5 2007 The inhibitory effects of the nitrogen-containing BPs (including alendronate, risedronate, ibandronate, and zoledronate) on osteoclasts appear to result from their inhibition of farnesyl pyrophosphate synthase (FPPS), a key branch-point enzyme in the mevalonate pathway. Diphosphonates 50-53 farnesyl diphosphate synthase Homo sapiens 211-215 17959891-1 2007 Nitrogen-containing bisphosphonates (nBPs) are bone-specific agents that inhibit farnesyl diphosphate synthase. Diphosphonates 20-35 farnesyl diphosphate synthase Homo sapiens 81-110 22460750-3 2007 For nitrogen-containing bisphosphonates there is a correlation between in vitro potency of inhibition of a specific enzyme, farnesyl pyrophosphate synthase, and their antiresorptive potency in vivo. Diphosphonates 24-39 farnesyl diphosphate synthase Homo sapiens 124-155 17291279-5 2007 Vgamma2Vdelta2 T cells can also recognize high levels of IPP in certain tumors and in cells treated with pharmacological agents, such as bisphosphonates and alkylamines, that block farnesyl pyrophosphate synthase. Diphosphonates 137-152 farnesyl diphosphate synthase Homo sapiens 181-212 17277961-15 2007 The more active nitrogen containing bisphosphonates inhibit mevalonate metabolism due to the specific inhibition of farnesyl pyrophosphate synthase. Diphosphonates 36-51 farnesyl diphosphate synthase Homo sapiens 116-147 16650801-2 2006 Although several years ago the molecular target of the potent nitrogen-containing BPs (N-BPs) was identified as farnesyl diphosphate synthase, an enzyme in the mevalonate pathway, recent data have shed new light on the precise mechanism of inhibition and demonstrated that the acute-phase reaction, an adverse effect of N-BPs, is also caused by inhibition of this enzyme. Diphosphonates 82-85 farnesyl diphosphate synthase Homo sapiens 112-141 16956297-3 2006 Bisphosphonates, pyrophosphate analogues in which the oxygen bridge between the two phosphorus atoms has been replaced by a carbon substituted with different side chains, are able to inhibit the FPPS enzyme. Diphosphonates 0-15 farnesyl diphosphate synthase Homo sapiens 195-199 16956297-4 2006 Moreover, nitrogen-containing bisphosphonates have been proposed as carbocation transition state analogues of FPPS. Diphosphonates 30-45 farnesyl diphosphate synthase Homo sapiens 110-114 17090032-3 2006 Here, we report the results of a solid-state (13)C, (15)N, and (31)P magic-angle sample spinning (MAS) NMR and quantum chemical investigation of several bisphosphonates, both as pure compounds and when bound to FPPS, to provide information about side-chain and phosphonate backbone protonation states when bound to the enzyme. Diphosphonates 153-168 farnesyl diphosphate synthase Homo sapiens 211-215 17090032-4 2006 We then used computational docking methods (with the charges assigned by NMR) to predict how several bisphosphonates bind to FPPS. Diphosphonates 101-116 farnesyl diphosphate synthase Homo sapiens 125-129 17062705-5 2006 RESULTS: Nitrogen-containing bisphosphonates act intracellularly by inhibiting farnesyl diphosphate synthase, an enzyme of the mevalonate pathway, thereby preventing prenylation of small GTPase signaling proteins required for normal cellular function. Diphosphonates 29-44 farnesyl diphosphate synthase Homo sapiens 79-108 17062705-6 2006 Inhibition of farnesyl diphosphate synthase also seems to account for their antitumor effects observed in vitro and for the activation of gamma,delta T cells, a feature of the acute-phase response to bisphosphonate treatment in humans. Diphosphonates 200-214 farnesyl diphosphate synthase Homo sapiens 14-43 16684881-2 2006 Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. Diphosphonates 70-85 farnesyl diphosphate synthase Homo sapiens 180-211 16684881-2 2006 Because of their bone-selective pharmacokinetics, nitrogen-containing bisphosphonates (N-BPs), currently used as clinical inhibitors of bone-resorption diseases, target osteoclast farnesyl pyrophosphate synthase (FPPS) and inhibit protein prenylation. Diphosphonates 70-85 farnesyl diphosphate synthase Homo sapiens 213-217