PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30205091-2 2018 Methadone undergoes N-demethylation by multiple cytochrome P450 (CYP) enzymes including CYP3A4, CYP2B6, CYP2C19, CYP2D6, CYP2C9, and CYP2C8. Nitrogen 20-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 113-119 3921236-11 1985 Studies with space-filling models of the drugs the metabolism of which is associated with debrisoquine 4-hydroxylase in the literature indicated that all can be fitted to a general structure in which a basic nitrogen is about 5 A away from the site of carbon hydroxylation and a hydrophobic domain is near the site of hydroxylation. Nitrogen 208-216 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 90-116 33479614-6 2020 This study establishes that CYP2D6-expressing live yeast cells can be a powerful tool for the enzymatic C-N, C-C bond cleavage of amino-acids. Nitrogen 106-107 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 28-34 30312494-0 2019 Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients. Nitrogen 56-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 30312494-0 2019 Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients. Nitrogen 56-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 30312494-0 2019 Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients. Nitrogen 56-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 30312494-0 2019 Significantly lower CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine metabolic ratio in carriers of CYP2D6*41 versus CYP2D6*9 or CYP2D6*10: a study on therapeutic drug monitoring data from 1003 genotyped Scandinavian patients. Nitrogen 56-57 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 110-116 30312494-11 2019 CONCLUSIONS: CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Nitrogen 2-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 13-19 30312494-11 2019 CONCLUSIONS: CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Nitrogen 2-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 129-135 30312494-11 2019 CONCLUSIONS: CYP2D6 metabolism measured as the O/N-desmethylvenlafaxine ratio is significantly lower in Scandinavian carriers of CYP2D6*41 vs. CYP2D6*9-10. Nitrogen 2-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 129-135 25475885-4 2015 In vitro analyses using liver microsomes from individual humans in correlation assays and recombinantly expressed P450 enzymes revealed that CYP2D6 was the major contributor to mirtazapine 8-hydroxylation with high affinity, and that CYP3A5 catalyzed N-demethylation in a similar high-capacity manner to that of CYP3A4. Nitrogen 251-252 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 141-147 29881433-6 2018 The N-demethylation pathway was indirectly affected by CYP2D6 phenotypic differences. Nitrogen 4-5 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 26456786-9 2015 Using human CYPs, CYP1A2, CYP2C19, CYP2D6, and/or CYP3A4 were found to catalyze N-oxide formation and N-, O-demethylation and/or oxidation. Nitrogen 80-81 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 35-41 26856397-5 2016 Olanzapine N-demethylation and N-oxygenation were found to be catalyzed by CYP1A2 and CYP2D6 and by CYP2D6 and FMO3, respectively, in experiments using liver microsomes and recombinant enzymes. Nitrogen 11-12 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 86-92 26856397-5 2016 Olanzapine N-demethylation and N-oxygenation were found to be catalyzed by CYP1A2 and CYP2D6 and by CYP2D6 and FMO3, respectively, in experiments using liver microsomes and recombinant enzymes. Nitrogen 11-12 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 100-106 23640382-4 2013 CYP2D6 showed a preference for catalyzing N-demethylation of d-DMA, and the intrinsic clearance (Clint) ratio of d-isomer to l-isomer was 1.41. Nitrogen 42-43 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 24010633-11 2014 The major metabolites of metoclopramide were N-hydroxylation and N-deethylation formed most efficiently by CYP2D6 but also formed by all CYPs examined. Nitrogen 45-46 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 24010633-11 2014 The major metabolites of metoclopramide were N-hydroxylation and N-deethylation formed most efficiently by CYP2D6 but also formed by all CYPs examined. Nitrogen 65-66 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 19601803-5 2009 Typical CYP2D6 substrates are usually lipophilic bases with a planar hydrophobic aromatic ring and a nitrogen atom which can be protonated at physiological pH, but several atypical substrates such as spirosulfonamide and pactimibe do not contain a basic nitrogen atom. Nitrogen 101-109 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 23361230-10 2013 They were also involved in the N-demethylation of the analogue methamphetamine and CYP2C19, CYP2D6, and CYP3A4 in its ring hydroxylation. Nitrogen 31-32 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 92-98 22459173-1 2012 Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily responsible for biotransformation of about 20% of drugs of known metabolism containing a basic nitrogen and a planar aromatic ring. Nitrogen 166-174 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 6-25 22459173-1 2012 Human cytochrome P450 2D6 (CYP2D6) is an enzyme of the CYP superfamily responsible for biotransformation of about 20% of drugs of known metabolism containing a basic nitrogen and a planar aromatic ring. Nitrogen 166-174 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 27-33 23552177-1 2013 The human cytochrome P450 2D6 (CYP2D6) is one of the major human drug metabolizing enzymes and acts preferably on substrates containing a basic nitrogen atom. Nitrogen 144-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 10-29 23552177-1 2013 The human cytochrome P450 2D6 (CYP2D6) is one of the major human drug metabolizing enzymes and acts preferably on substrates containing a basic nitrogen atom. Nitrogen 144-152 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 31-37 22372551-4 2012 All four contain planar, aromatic groups as well as basic nitrogens common to CYP2D6 substrates. Nitrogen 58-67 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 78-84 19601803-5 2009 Typical CYP2D6 substrates are usually lipophilic bases with a planar hydrophobic aromatic ring and a nitrogen atom which can be protonated at physiological pH, but several atypical substrates such as spirosulfonamide and pactimibe do not contain a basic nitrogen atom. Nitrogen 254-262 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 17764997-1 2008 Cytochrome P450 CYP2D6 is involved in the oxidation of well over 150 drugs and, in general, those which contain a basic nitrogen atom in the molecule. Nitrogen 120-128 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 16-22 18524873-1 2008 Typical CYP2D6 substrates generally contain a basic nitrogen atom that interacts with Asp(301) and/or Glu(216) and an aromatic moiety adjacent to the site of metabolism. Nitrogen 52-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 18524873-9 2008 The effect of the N-alkyl chain length of pactimibe analogs on their CYP2D6 metabolic stability was plausibly explained by the docking model. Nitrogen 18-19 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 69-75 19645588-5 2009 Typical CYP2D6 substrates are usually lipophilic bases with an aromatic ring and a nitrogen atom, which can be protonated at physiological pH. Nitrogen 83-91 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 18725510-0 2008 The molecular basis of CYP2D6-mediated N-dealkylation: balance between metabolic clearance routes and enzyme inhibition. Nitrogen 39-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 23-29 18725510-3 2008 The CYP2D6 pharmacophore and characteristic features in the active site cavity suggest a favored substrate orientation that prevents N-dealkylation from occurring. Nitrogen 133-134 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 4-10 18725510-4 2008 In this study, the literature was searched for N-dealkylated and non-N-dealkylated CYP2D6 substrates. Nitrogen 69-70 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 83-89 16510126-5 2006 The apparent Km value of CYP2D6 was close to that for 5-MeO-DIPT O-demethylation, and the Km values of other CYP enzymes were similar to those of the low-Km (CYP2C19), intermediate-Km (CYP1A2, CYP2C8 and CYP3A4) and high-Km phases (CYP2C9), respectively, for N-deisopropylation in human liver microsomes. Nitrogen 259-260 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 17020955-7 2007 In human liver microsomes, involvement of CYP2D6, CYP1A2, CYP2C9, and CYP2C19 in diphenhydramine N-demethylation was confirmed by using P450 isozyme-specific inhibitors. Nitrogen 97-98 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 11504269-8 2001 The rate of other metabolic routes mediated by CYP2D6 only corresponded to about one fifth of the CYP2D6 catalyzed N-demethylation rate. Nitrogen 115-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 98-104 16272405-3 2006 The results indicate that CYP1A2 and CYP3A4 are the main enzymes responsible for 5-sulfoxidation and N-demethylation (34-52%), whereas CYP2D6 is the basic enzyme that catalyzes mono-2- and di-2-sulfoxidation of thioridazine in human liver (49 and 64%, respectively). Nitrogen 101-102 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 16269134-2 2005 The T309V mutant of CYP2D6 displayed a strong shift from O-dealkylation to N-dealkylation reactions in oxidation of dextromethorphan and 3,4-methylenedioxymethylamphetamine. Nitrogen 75-76 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 20-26 15365656-9 2004 CONCLUSION: CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyze LOP N-demethylation in human liver microsomes, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP. Nitrogen 2-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 28-34 14992686-1 2004 Although the residues that determine the preference of CYP2D6 (cytochrome P450 2D6) for compounds containing a basic nitrogen are well characterized, the contribution of other active site residues to substrate binding and orientation is less well understood. Nitrogen 117-125 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 55-61 14992686-1 2004 Although the residues that determine the preference of CYP2D6 (cytochrome P450 2D6) for compounds containing a basic nitrogen are well characterized, the contribution of other active site residues to substrate binding and orientation is less well understood. Nitrogen 117-125 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 63-82 12446689-2 2003 CYP2D6 substrates typically contain a basic nitrogen atom, and the active-site residue Asp-301 has been implicated in substrate recognition through electrostatic interactions. Nitrogen 44-52 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-6 12446689-12 2003 Neutralizing both Glu-216 and Asp-301 thus effectively alters substrate recognition illustrating the central role of the negative charges provided by both residues in defining the specificity of CYP2D6 toward substrates containing a basic nitrogen. Nitrogen 239-247 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 195-201 12433806-3 2002 Kinetics evidence is presented that the N-depropylation of (-)-OSU6162 in human hepatic microsomes is mediated by multiple cytochrome p450 (p450) enzymes, in particular CYP2D6. Nitrogen 40-41 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 169-175 11602510-0 2001 Characterization of dextromethorphan O- and N-demethylation catalyzed by highly purified recombinant human CYP2D6. Nitrogen 44-45 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 107-113 11504269-8 2001 The rate of other metabolic routes mediated by CYP2D6 only corresponded to about one fifth of the CYP2D6 catalyzed N-demethylation rate. Nitrogen 115-116 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 16432914-7 2006 A computer-assisted simulation study using energy minimization and molecular dynamics techniques indicated that the hydrophobic interaction of an aromatic moiety of the substrate with Phe-120 and the ionic interaction of a basic nitrogen atom of the substrate with Glu-222 in combination with Glu-216 play important roles in the binding of BF and BTL by CYP2D6 and the orientation of these substrates in the active-site cavity. Nitrogen 229-237 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 354-360 16135359-2 2005 Typical CYP2D6 substrates generally contain a basic nitrogen atom and an aromatic moiety adjacent to the site of metabolism. Nitrogen 52-60 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 8-14 15585365-6 2005 The results show that CYP3A4 contributes to the oxidation of KR-60436 to pyrrole-KR-60436, O-demethylpyrrole-KR-60436 and N-dehydroxyethyl-KR-60436, and CYP2C9 and CYP2D6 play roles in demethylation of KR-60436 to form the active metabolite, O-demethyl-KR-60436. Nitrogen 122-123 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 164-170 11095593-7 2000 Interestingly, due to the higher fluorescent yield of the N-alkyl metabolites compared with the metabolite of MAMC, O-dealkylation of N-methyl MAMC by CYP2D6 can be measured with a more than 3-fold higher sensitivity. Nitrogen 58-59 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 151-157 11519155-2 2001 Cytochrome P450(CYP) 2D6 is involved in the hydroxylation of TCAs, while N-demethylation of TCAs is mediated by other such as CYP2C19, 3A4 and 1A2. Nitrogen 73-74 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-24 10421623-8 1999 These observations suggested that the N-demethylation of azelastine is most extensively catalyzed by the CYP2D6 and 3A4 isoforms in humans. Nitrogen 38-39 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 105-111 11102743-7 2000 To further demonstrate the usefulness of the HTS-assay, IC(50) values of a series of five N-substituted analogs of 3, 4-methylenedioxyamphetamine for CYP2D6 have been determined. Nitrogen 90-91 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 150-156 10752644-6 2000 Subsequently, it was determined that AMA, DAA and MPA also underwent CYP2D6-catalysed N-dealkylation. Nitrogen 86-87 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 69-75 10359460-8 1999 This apparent involvement of CYP2D6 in the N-demethylation of CLZ did not corroborate with the findings of other experiments. Nitrogen 43-44 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 29-35 9560305-1 1998 Cytochrome P-450 CYP2D6, human debrisoquine hydroxylase, metabolizes more than 30 prescribed drugs, the vast majority of which are small molecules containing a basic nitrogen atom. Nitrogen 166-174 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 17-23 10493260-2 1999 Although CYP2D6 substrates are structurally diverse, most are small molecules that interact with the protein via an electrostatic interaction between a basic nitrogen which is common to the majority of CYP2D6 substrates and an aspartic acid residue in the active site of the protein. Nitrogen 158-166 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 9-15 10493260-2 1999 Although CYP2D6 substrates are structurally diverse, most are small molecules that interact with the protein via an electrostatic interaction between a basic nitrogen which is common to the majority of CYP2D6 substrates and an aspartic acid residue in the active site of the protein. Nitrogen 158-166 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 202-208 9733666-3 1998 An overlay of terfenadine and dextromethorphan, a known substrate of CYP2D6, showed that it was possible to superimpose the site of hydroxylation (t-butyl group) and the nitrogen atom of terfenadine with similar regions in dextromethorphan. Nitrogen 170-178 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 69-75 9143866-8 1997 CONCLUSION: It seems that there was a good correspondence between the capacity of drugs to inhibit the O- and N-demethylation of codeine in human liver microsomes and their apparent metabolism by CYP2D6 or CYP3A4, respectively in vivo in man, suggesting that this in vitro inhibition test may be a useful screen for drugs which interact with these two important drug-metabolising enzymes. Nitrogen 2-3 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 196-202 9311621-5 1997 This was confirmed by studies with recombinant CYP2D6 expressed in yeast, which was also shown to effect the N-demethylation of MeAmp. Nitrogen 109-110 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 47-53 9110356-1 1997 Using in vitro techniques, the present study demonstrates that CYP2D6, and 3A4 are involved in N-demethylation of citalopram (CIT) enantiomers. Nitrogen 95-96 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 63-69 9143866-1 1997 OBJECTIVE: The O- and N-demethylation of codeine is catalysed by CYP2D6 and CYP3A4 respectively. Nitrogen 22-23 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 65-71 8877032-0 1996 Variable contribution of CYP2D6 to the N-dealkylation of S-(-)-propranolol by human liver microsomes. Nitrogen 39-40 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 25-31 8877032-6 1996 The two livers with the highest proportion of CYP2D6-mediated N-dealkylation had relatively high ratios of specific CYP2D6 to CYP1A2 activity. Nitrogen 62-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 46-52 8877032-6 1996 The two livers with the highest proportion of CYP2D6-mediated N-dealkylation had relatively high ratios of specific CYP2D6 to CYP1A2 activity. Nitrogen 62-63 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 116-122 8660692-1 1996 Cytochrome P450 2D6 (CYP2D6) catalyzes the oxidation of substrates with a positively charged nitrogen atom 5-7 angstroms from the site of the oxidation. Nitrogen 93-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 0-19 8660692-1 1996 Cytochrome P450 2D6 (CYP2D6) catalyzes the oxidation of substrates with a positively charged nitrogen atom 5-7 angstroms from the site of the oxidation. Nitrogen 93-101 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 8627546-4 1996 The kinetics of the N-demethylation of MPTP (1 microM - 3 mM) by microsomes from the liver of an extensive metabolizer with respect to cytochrome P4502D6 (CYP2D6) activity were biphasic (apparent Km1 and Km2 values = 48 and 2882 microM). Nitrogen 20-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-153 8764331-7 1996 Among the recombinant human CYP isoforms, CYP2D6, 2B6, 3A4 and 1A2 catalyzed the 8-hydroxylation, and CYP1A2 and 3A4 were involved exclusively in the N-oxidation, whereas CYP2B6, 2C19, 1A2, 3A4 and 2D6 showed a catalytic activity for the N-demethylation, for either or both of MS enantiomers. Nitrogen 150-151 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 42-48 8627546-4 1996 The kinetics of the N-demethylation of MPTP (1 microM - 3 mM) by microsomes from the liver of an extensive metabolizer with respect to cytochrome P4502D6 (CYP2D6) activity were biphasic (apparent Km1 and Km2 values = 48 and 2882 microM). Nitrogen 20-21 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 155-161 8712396-5 1996 Rates of N-dealkylated metabolite formation significantly correlated with nifedipine oxidation activity (a marker of CYP3A4 activity) for fentanyl and sufentanil (r = 0.93 and 0.87, n = 18, respectively), but not with the oxidation activity for ethoxyresorufin (CYP1A2), S-mephenytoin (CYP2C19), bufuralol (CYP2D6), or chlorzoxazone (CYP2E1). Nitrogen 9-10 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 307-313 7756104-6 1995 The immunoidentified CYP2D6 and CYP3A4 correlated with the rates of O-deethylation (r = 0.972) and N-demethylation (r = 0.969), respectively. Nitrogen 99-100 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 21-27 34648192-5 2022 RESULTS: The experiments in supersomes revealed CYP1A2 as the major CYP for 4-MAA N-demethylation and 4-FAA formation with CYP2C19 and CYP2D6 contributing to N-demethylation. Nitrogen 158-159 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 135-141 1510710-8 1992 Negligible metabolism of tolbutamide and S-mephenytoin, substrates of the 2C sub-family, and of p-nitrophenol, a substrate of CYP2E1, was detected, although a trace of the N-deethylated metabolite of lignocaine, thought to be metabolised by CYP3A4, was detected with microsomes from CYP2D6-expressing yeast cells. Nitrogen 0-1 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 283-289 35179893-2 2022 Introducing a nitrogen atom into the aromatic portion of the tetrahydroisoquinoline ring led to several heterocyclic variants including the 5,6,7,8-tetrahydro-1,6-naphthyridine series, greatly reducing the inhibition of the CYP 2D6 enzyme. Nitrogen 14-22 cytochrome P450 family 2 subfamily D member 6 Homo sapiens 224-231