PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 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 B member 6 Homo sapiens 171-177 9698292-9 1998 Therefore, the N-demethylation of (S)-MP to nirvanol may be a useful means of probing the activity of CYP2B6 in vitro when concentrations of >1000 microM are used, but it is unlikely to be a suitable phenotyping tool for this isoform in vivo, where concentrations of >1000 microM are rarely encountered. Nitrogen 15-16 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 102-108 8330339-1 1993 We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Nitrogen 263-264 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 112-116 8886603-12 1996 Taken together, these studies indicate that the N-demethylation of S-mephenytoin by human liver microsomes is catalyzed primarily by CYP2B6. Nitrogen 48-49 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 133-139 8274159-8 1993 Whereas the N-hydroxylation of the guanidine involves the usual monooxygenase activity of cytochrome P450 the resultant N-hydroxyguanidine decouples monooxygenases (cytochrome P450, FMO) and the H2O2 and, above all, O2- thus formed transform the N-hydroxyguanidine further to the corresponding urea derivative. Nitrogen 12-13 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 101-105 8274159-8 1993 Whereas the N-hydroxylation of the guanidine involves the usual monooxygenase activity of cytochrome P450 the resultant N-hydroxyguanidine decouples monooxygenases (cytochrome P450, FMO) and the H2O2 and, above all, O2- thus formed transform the N-hydroxyguanidine further to the corresponding urea derivative. Nitrogen 12-13 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 176-180 8902262-4 1996 All drugs metabolized by P450 2D6 contain a basic nitrogen atom, and a flat hydrophobic region coplanar to the oxidation site which is either 5 or 7 A away from the basic nitrogen atom. Nitrogen 50-58 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 25-29 8902262-4 1996 All drugs metabolized by P450 2D6 contain a basic nitrogen atom, and a flat hydrophobic region coplanar to the oxidation site which is either 5 or 7 A away from the basic nitrogen atom. Nitrogen 171-179 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 25-29 8274159-0 1993 Cytochrome P450 dependent N-hydroxylation of a guanidine (debrisoquine), microsomal catalysed reduction and further oxidation of the N-hydroxy-guanidine metabolite to the urea derivative. Nitrogen 26-27 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 11-15 8423765-13 1993 Both CYP1A2 and CYP3A4 catalyzed N-dealkylation of propafenone, with specific activities of 0.32 pmol/min/pmol of P450 and 0.16 pmol/min/pmol of P450, respectively. Nitrogen 33-34 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 114-118 8423765-0 1993 Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Nitrogen 79-80 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 54-58 8423765-13 1993 Both CYP1A2 and CYP3A4 catalyzed N-dealkylation of propafenone, with specific activities of 0.32 pmol/min/pmol of P450 and 0.16 pmol/min/pmol of P450, respectively. Nitrogen 33-34 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 145-149 32817462-3 2020 We hypothesized that NO or derivative reactive nitrogen species may generate adducts of tyrosine and/or cysteine residues, causing CYP2B6 downregulation, and selected Tyr and Cys residues for mutation based on predicted solvent accessibility. Nitrogen 47-55 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 131-137 32817462-9 2020 We propose that cumulative nitrations of Y190, Y317, and Y380 by reactive nitrogen species cause destabilization of CYP2B6, which may act synergistically with heme nitrosylation to target the enzyme for degradation. Nitrogen 74-82 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 116-122 1794978-6 1991 These findings suggest that epsilon-amino nitrogen of Lys-301, which was introduced by amino acid substitution, occupies the 6th coordination position with the heme iron of the Lys-mutated P450, because, owing to conformation of the P450 protein, the epsilon-amino group may be located at just the right position for coordination as the internal 6th ligand. Nitrogen 42-50 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 189-193 1794978-6 1991 These findings suggest that epsilon-amino nitrogen of Lys-301, which was introduced by amino acid substitution, occupies the 6th coordination position with the heme iron of the Lys-mutated P450, because, owing to conformation of the P450 protein, the epsilon-amino group may be located at just the right position for coordination as the internal 6th ligand. Nitrogen 42-50 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 233-237 30902024-8 2020 The catalytic efficiency (kcat/Km) for meperidine N-demethylation was similar between recombinant CYP2B6 and CYP2C19, but markedly lower by CYP3A4. Nitrogen 50-51 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 98-104 30902024-14 2020 These findings demonstrate that the relative CYP3A4, CYP2B6, and CYP2C19 involvement in meperidine N-demethylation depends on the enzyme activities in individual human liver microsomal samples. Nitrogen 99-100 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 53-59 26276083-6 2015 Studies showed the involvement of CYP1A2, CYP2B6, CYP2C19, and CYP3A4 in N-dealkylation of all three compounds and additionally CYP2D6 for lefetamine and NEDPA. Nitrogen 73-74 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 42-48 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 B member 6 Homo sapiens 96-102 31375472-2 2019 The assay was created to develop physiologically relevant P450 inhibition information, taking advantage of the complete organelle composition and their associated drug-metabolizing enzymes of the MMHH but with the ease of use of human liver microsomes, including storage at -80 C instead of in liquid nitrogen, and thaw and use without centrifugation and microscopic evaluation as required for intact hepatocytes. Nitrogen 301-309 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 58-62 30589555-7 2019 This investigation evaluated halogen substitution effects on CYP2B6-catalyzed ketamine analogs N-demethylation in vitro and modeled interactions with CYP2B6 using various computational approaches. Nitrogen 95-96 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 61-67 27185541-4 2016 The observed phase-I metabolites were formed through N-deethylation, N,N-deethylation, N-hydroxylation, and de-esterification, with CYP2B6 and CYP2C19 being the main enzymes catalyzing their formation. Nitrogen 53-54 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 132-138 24477223-7 2014 Univariant and multivariant analysis indicated associations for CYP2B6 g.18492T>C (p < 0.001 and p = 0.001), aspartate aminotransferase (AST; p = 0.001 and p = 0.006) and blood urea nitrogen (BUN; p = 0.011 and p = 0.016) with plasma efavirenz concentration. Nitrogen 188-196 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 64-70 23550066-0 2013 The CYP2B6*6 allele significantly alters the N-demethylation of ketamine enantiomers in vitro. Nitrogen 45-46 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 4-10 23592585-0 2013 How is a metabolic intermediate formed in the mechanism-based inactivation of cytochrome P450 by using 1,1-dimethylhydrazine: hydrogen abstraction or nitrogen oxidation? Nitrogen 150-158 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 89-93 23774830-6 2013 The enzyme kinetic studies showed that the initial metabolic step in humans, the N-deethylation, was catalyzed by CYP2B6 and CYP3A4. Nitrogen 81-82 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 114-120 23298862-6 2013 Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6.6 and CYP2B6.1 was determined. Nitrogen 34-35 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 75-81 23298862-13 2013 Diminished methadone N-demethylation by CYP2B6.6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6*6 polymorphism. Nitrogen 21-22 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 174-180 23298862-6 2013 Methadone enantiomer and racemate N-demethylation by recombinant-expressed CYP2B6.6 and CYP2B6.1 was determined. Nitrogen 34-35 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 88-94 23298862-13 2013 Diminished methadone N-demethylation by CYP2B6.6 may provide a mechanistic explanation for clinical observations of altered methadone disposition in individuals carrying the CYP2B6*6 polymorphism. Nitrogen 21-22 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 40-46 23361846-7 2013 CYP2B6 inhibition reduces methadone N-demethylation and clearance, and alters methadone concentrations, demonstrating an important role for CYP2B6 in clinical methadone disposition. Nitrogen 36-37 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 22349139-11 2012 Assays with recombinant CYPs verified that the N-demethylation is catalysed by CYP3A4, CYP2C19 and CYP2B6. Nitrogen 47-48 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 99-105 22511698-2 2012 Methadone is primarily metabolized by N-demethylation to an inactive metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP) by CYP3A4 and CYP2B6. Nitrogen 38-39 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 151-157 18563875-6 2008 The calculations show that azole binding is a stepwise mechanism whereby first the water molecule from the resting state of P450 is released from the sixth binding site of the heme to create a pentacoordinated active site followed by coordination of the azole nitrogen to the heme iron. Nitrogen 260-268 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 124-128 22023129-7 2011 For all 3 species, inhibitors of CYP3A4, CYP2A6, CYP2C19, CYP2B6, and CYP2C9 diminished N-demethylation of ketamine. Nitrogen 88-89 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 58-64 19089010-1 2009 The mechanism of N-dealkylation of N-cyclopropyl-N-methylaniline () catalyzed by cytochrome P450 (P450) was investigated using density functional theory. Nitrogen 17-18 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 81-103 18725511-7 2008 The highest contribution for the N-demethylation as calculated from the enzyme kinetic data, were obtained for CYP2B6 (R,S-MDMA), CYP1A2 (R-MDMA), and CYP2B6 (S-MDMA). Nitrogen 33-34 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 111-117 18725511-7 2008 The highest contribution for the N-demethylation as calculated from the enzyme kinetic data, were obtained for CYP2B6 (R,S-MDMA), CYP1A2 (R-MDMA), and CYP2B6 (S-MDMA). Nitrogen 33-34 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 151-157 15686361-0 2005 P(450)/NADPH/O(2)- and P(450)/PhIO-catalyzed N-dealkylations are mechanistically distinct. Nitrogen 7-8 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 18292673-7 2008 METHODS: N-demethylation of racemic methadone and individual enantiomers by expressed CYPs 2B6, 2C19, and 3A4 was evaluated. Nitrogen 9-10 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 86-100 17259447-3 2007 N-Demethylation of methadone in vitro is predominantly mediated by cytochrome P450 CYP3A4 and CYP2B6 and somewhat by CYP2C19. Nitrogen 0-1 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 94-100 17259447-4 2007 This investigation evaluated stereoselectivity, models, and kinetic parameters for methadone N-demethylation by recombinant CYP2B6, CYP3A4, and CYP2C19, and the potential for interactions between enantiomers during racemate metabolism. Nitrogen 93-94 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 124-130 16214851-2 2006 Various bioactivating enzymes, such as cytochromes P450 and myeloperoxidase, have been shown to be capable of catalyzing the N-oxidation of these compounds. Nitrogen 125-126 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 51-75 18292673-10 2008 RESULTS: At clinical concentrations, methadone enantiomer N-demethylation by recombinant CYPs 2B6, 3A4, and 2C19 was S > R, S = R, and S << R. Greater stereoselective metabolism (S > R) occurred in livers expressing high levels of CYP2B6 compared with CYP3A4. Nitrogen 58-59 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 243-249 15821045-1 2005 Ifosfamide nephrotoxicity is attributed to the formation of a toxic metabolite, chloroacetaldehyde, via N-dechloroethylation, a reaction that is purportedly catalyzed by CYP3A and CYP2B6. Nitrogen 104-105 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 180-186 15078194-5 2004 Metabolic activation occurs by N-hydroxylation, a reaction catalyzed by cytochromes p450 (CYP). Nitrogen 31-32 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 84-88 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 B member 6 Homo sapiens 12-18 15319333-0 2004 CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Nitrogen 61-62 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 12527701-5 2003 Fluorometry was used to measure N-alkylPP formation following interaction of porphyrinogenic xenobiotics and NADPH with cDNA-expressed human P450 enzymes in microsomes from HLCL or BIICL. Nitrogen 32-33 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 141-145 12844133-9 2003 CONCLUSIONS: These results indicate that artemisinin induces the N-demethylation of S-mephenytoin probably by an increased capacity of CYP2B6. Nitrogen 2-3 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 135-141 12975333-11 2003 A mechanism for the p450-mediated ring scission is proposed in which the isoxazole ring nitrogen or oxygen coordinates to the reduced form of the heme followed by charge transfer from p450Fe(II) to the C=N bond or deprotonation of the C3-H, which results in a cleavage of the N-O bond. Nitrogen 88-96 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 20-24 12721102-17 2003 The highest intrinsic clearance (V(max)/K(m)) was found for CYP1A subfamily, CYP3A4 and CYP2B6 in the case of 5- sulphoxidation, and for CYP2C19, CYP1A subfamily and CYP2B6 in the case of N-demethylation. Nitrogen 188-189 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 88-94 10692561-0 2000 Role of human liver microsomal CYP3A4 and CYP2B6 in catalyzing N-dechloroethylation of cyclophosphamide and ifosfamide. Nitrogen 63-64 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 42-48 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 B member 6 Homo sapiens 134-138 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 B member 6 Homo sapiens 140-144 12351147-1 2002 N-oxidation by cytochrome p450 enzymes is an initial step in the metabolic activation of aromatic amine compounds. Nitrogen 0-1 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 26-30 11396966-0 2001 Differential N-demethylation of l-alpha-acetylmethadol (LAAM) and norLAAM by cytochrome P450s 2B6, 2C18, and 3A4. Nitrogen 13-14 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 77-103 11259560-4 2001 For the pathways of N-demethylation (mediated by CYPs 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) and E-10 hydroxylation (mediated by CYPs 2B6, 2D6, and 3A4), the model-predicted biotransformation rates in microsomes from a panel of 12 human livers determined from enzyme kinetic parameters of the recombinant CYPs were similar to, and correlated with the observed rates. Nitrogen 20-21 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 130-143 10799653-8 2000 The most important isozyme for this reaction appeared to be CYP2B6, the microsomal content of which was found to be strongly correlated to N-deethylation of MDE (r(s) = 0.90; P < 0.001). Nitrogen 139-140 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 60-66 12519691-10 2003 However, other cytochrome P450 enzymes (CYP2E1 and CYP2B6) also appear to play a role in the N-oxidation of this drug. Nitrogen 93-94 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 51-57 15618670-4 2002 CYP2B6 had a higher affinity for both N-depropagylation (K(m)=21.4 microM) and N-demethylation (K(m)=25.2 microM) of selegiline than CYP3A4 and CYP1A2. Nitrogen 38-39 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 11353758-0 2001 Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Nitrogen 1-2 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 15-21 11353758-5 2001 Among the 12 cDNA-expressed CYP enzymes examined, CYP2B6, CYP2C9, and CYP3A4 showed high activities for the N-demethylation of both enantiomers at the substrate concentration of 1 mM. Nitrogen 15-16 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 50-56 11353758-6 2001 CYP2B6 had the lowest K(m) value for the N-demethylation of (R)- and (S)-ketamine (74 and 44 microM, respectively). Nitrogen 41-42 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 11353758-7 2001 Also, the intrinsic clearance (CL(int): V(max)/K(m)) of CYP2B6 for the N-demethylation of both enantiomers were 7 to 13 times higher than those of CYP2C9 and CYP3A4. Nitrogen 71-72 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 56-62 11353758-11 2001 CYP2B6 mainly mediates the N-demethylation of (R)- and (S)-ketamine in human liver microsomes at therapeutic concentrations (5 microM). Nitrogen 27-28 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 0-6 10692561-6 2000 Because CYP2B6 can make a significant contribution to human liver microsomal IFA N-dechloroethylation, but only a minor contribution to IFA 4-hydroxylation, the selective inhibition of hepatic CYP2B6 activity in individuals with a high hepatic CYP2B6 content may provide a useful approach to minimize the formation of therapeutically inactive but toxic N-dechloroethylated IFA metabolites. Nitrogen 81-82 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 8-14 10534317-11 1999 The overall extent of IFA N-dechloroethylation varied with the CYP3A4 and CYP2B6 content of each liver, but was significantly lower for R-IFA (32 +/- 13%) than for S-IFA (62 +/- 17%, n = 8; p <.001) in all livers examined. Nitrogen 26-27 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 74-80 10570024-3 1999 The apparent K(m) values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 microM). Nitrogen 71-72 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 124-130 10570024-6 1999 Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes. Nitrogen 67-68 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 27-33 10101147-10 1999 The antibody also was found to immunoinhibit CYP2B6-catalyzed N-demethylation of (S)-mephenytoin in human liver microsomes by 68 to 79%. Nitrogen 62-63 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 45-51 10101149-0 1999 Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. Nitrogen 42-43 cytochrome P450 family 2 subfamily B member 6 Homo sapiens 8-14