ライフサイエンスコーパス: CYP2B6

1 tion could affect drug-mediated induction of CYP2B6.

2 tocytes, is responsible for PHY induction of CYP2B6.

3 trations associated with potent induction of CYP2B6.

4 mediates optimal drug-induced expression of CYP2B6.

5 ty, with the most dramatic effects seen with CYP2B6.

6 l and mapping to CYP2A6, MAP3K10, ADCK4, and CYP2B6.

7 adation of the cytochrome P450 (P450) enzyme CYP2B6.

8 cient than 2-oxo-clopidogrel in inactivating CYP2B6.

9 n of the active metabolite of clopidogrel to CYP2B6.

10 ed that the -82T-->C substitution within the CYP2B6*22 allele creates a functional CCAAT/enhancer-bin

11 were genotyped for common variant alleles of CYP2B6, 2C19, 2C9, and 3A5.

12 a survival analysis, patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher proba

13 observed frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%,

14 Patients carrying the CYP2B6 516 TT genotype and slow-acetylation NAT2 phenoty

15 Models that included CYP2B6 516/983 genotype best predicted pharmacokinetics.

16 The composite CYP2B6 516/983 genotype was significantly associated wit

17 On the basis of the composite CYP2B6 516/983 genotype, the 34 participants comprised 1

18 ne may not differ substantially according to CYP2B6 516/983 genotype.

19 justed for body mass index and the composite CYP2B6 516/983 genotype.

20 r nevirapine elimination was associated with CYP2B6 516G --> T (P = .04).

21 th CYP2B6 983T --> C (P = .004) but not with CYP2B6 516G --> T (P = .8).

22 When stratified based on CYP2B6 516G>T (n = 29 ; 11 GG, 10 GT and 8 TT), efaviren

23 CYP2B6 516G>T was independently associated with efaviren

24 nificantly associated with the polymorphisms CYP2B6 516G-->T and CYP2C19 681G-->A, respectively.

25 5; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), M

26 omics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in bot

27 Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AU

28 pooled analysis and 315 ng/mL (108-1360) in CYP2B6 516TT group.

29 Among CYP2B6*6 allele carriers, patients with NR1I3 rs2502815T

30 etion, and TP53 deletion/mutation identified CYP2B6*6 and TP53 mutation/deletion as the only independ

31 try, longer time to IC50 was associated with CYP2B6 983T --> C (P = .004) but not with CYP2B6 516G --

32 ng single-dose nevirapine may be greater for CYP2B6 983T --> C than for 516G --> T and are less prono

33 Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected A

34 in could suppress drug-induced expression of CYP2B6 (a typical target gene of CAR) by modulating the

35 stitutive androstane receptor (hCAR) induces CYP2B6, a key enzyme responsible for CPA bioactivation.

36 ed relationships between 22 polymorphisms in CYP2B6, ABCB1, and CYP3A5; plasma efavirenz exposure; an

37 nalyses involved another 51 polymorphisms in CYP2B6, ABCB1, CYP3A4, and CYP3A5.

38 Polymorphisms in CYP2B6 affect the steady-state plasma concentrations of

39 Efavirenz is metabolized by CYP2B6, an inducible enzyme whose expression is regulate

40 ater on therapy than off therapy in 58% with CYP2B6 and 93% with NAT2 slow metabolizer genotypes.

41 sm-based inactivators; we use the example of CYP2B6 and bergamottin to illustrate the finer points of

42 e (WGA), derived from HepG2, which expresses CYP2B6 and CAR.

43 It induced the expression of CYP2B6 and caused the translocation of hCAR from the cyt

44 ct plasma efavirenz exposure were defined by CYP2B6 and CYP2A6 polymorphisms.

45 tive form of AMPK mimics the PB induction of CYP2B6 and CYP2B1 gene expression.

46 , CAR-, and PXR-mediated induction of CYP1A, CYP2B6 and CYP3A4 (for CAR and PXR), and CYP2C8 (for PXR

47 R3 is capable of transactivating the natural CYP2B6 and CYP3A4 gene enhancers, exhibiting both ligand

48 educes that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condit

49 in HepG2 cells, it induces the expression of CYP2B6 and CYP3A4, targets of hCAR and the pregnane X re

50 , PB significantly induces the expression of CYP2B6 and CYP3A4, two shared target genes of hCAR and h

51 bits expressions of CAR and its target genes CYP2B6 and CYP3A4.

52 the design of selective inhibitors of human CYP2B6 and for the development of drugs that avoid drug

53 In STRIDE, slow metabolizer CYP2B6 and NAT2 genotypes were each associated with incr

54 We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with p

55 In kinetic studies of BDE-47 metabolism by CYP2B6 and pooled HLMs, we found Km values ranging from

56 For kinetic studies, CYP2B6 and pooled human liver microsomes (HLMs) were inc

57 The induction of human CYP2B6 and the rat (CYP2B1) and mouse (Cyp2b10) homologu

58 Associations were characterized with CYP2B6 and UGT1A1 genotypes that affect efavirenz and IN

59 ng nicotine-metabolizing enzymes (CYP2A6 and CYP2B6) and nicotinic acetylcholine receptor subunits (C

60 of isoniazid and efavirenz metabolism (NAT2, CYP2B6) and other participant characteristics.

61 ansduced with the human cytochrome P450 gene CYP2B6 are greatly sensitized to CPA, however, the pathw

62 data to be normally distributed, except for CYP2B6, as some individuals completely lacked CYP2B6 mRN

63 nuclear factor 4 alpha (HNF4alpha) to induce CYP2B6 by phenobarbital (PB) in human primary hepatocyte

64 microsomes (which has been taken to indicate CYP2B6 catalysis), orphenadrine inhibited cDNA-expressed

65 2C9, 2D6, and 2E1) examined, only CYP1A2 and CYP2B6 could catalyze ortho hydroxylation of [o-3H]metho

66 Polymorphisms in CYP2B6, CYP2C19, CYP3A4, CYP3A5, and MDR1 were character

67 th corresponding increases in immunoreactive CYP2B6, CYP2C8, CYP2C9, and CYP3A4, all previously shown

68 plumbagin was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a no

69 The major enzymes detected were CYP1B1, CYP2B6, CYP2D6, and CYP3A4 with mean values of 2.5, 2.6,

70 software suggested a role of CYP1A2, CYP2A6, CYP2B6, CYP2E1, and CYP3A4 in the metabolism of chiral P

71 has been reported to be an inducer of human CYP2B6, CYP3A4, and murine CYP2C29.

72 ny of the CYP genes tested (CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP1A2).

73 ermines CAR-mediated activation of the human CYP2B6 (cytochrome P450 2B6) gene.

74 -chlorophenyl)imidazole blocked NO-dependent CYP2B6 degradation, suggesting that NO access to the act

75 tion of CYP2B6 protein but did not stimulate CYP2B6 degradation.

76 f tyrosine and/or cysteine residues, causing CYP2B6 downregulation, and selected Tyr and Cys residues

77 ule located -8.5 kilobases upstream from the CYP2B6 encoding region is described.

78 1I3 genotype on plasma EFV concentration and CYP2B6 enzyme activity among TB-HIV co-infected patients

79 R1I3 genes influence plasma EFV exposure and CYP2B6 enzyme activity in TB-HIV co-infected patients on

80 The CYP2B6 enzyme metabolizes commonly used therapeutics and

81 enhancer element that mediates induction of CYP2B6 expression by CAR.

82 Significant interindividual variability in CYP2B6 expression has been attributed to either genetic

83 m active chromatin complex during PB-induced CYP2B6 expression in human primary hepatocytes.

84 formin is a potent repressor of drug-induced CYP2B6 expression through specific inhibition of human C

85 Weight gain was similar in CYP2B6 extensive metabolizers in the efavirenz arm and i

86 Weight gain was similar between CYP2B6 extensive metabolizers in the efavirenz arm and i

87 CYP2B6 G516T and C485-18T polymorphisms were the most si

88 22 participants carried polymorphisms in the CYP2B6 gene associated with slow EFV metabolism.

89 The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in andr

90 a powerful system to study the regulation of CYP2B6 gene expression by PB.

91 is essential for mediating PHY induction of CYP2B6 gene expression.

92 ivator, to WGA and human hepatocytes induces CYP2B6 gene expression.

93 her, these observations demonstrate that the CYP2B6 gene is directly regulated by PXR and further est

94 Given that the CYP2B6 gene is primarily regulated by the constitutive a

95 onsive enhancer module (PBREM) region of the CYP2B6 gene, a 51-base-pair enhancer element that mediat

96 ite and enhances the basal expression of the CYP2B6 gene.

97 signal are necessary for CAR to activate the CYP2B6 gene.

98 the transcriptional regulation of the human CYP2B6 gene.

99 es the induction of the cytochrome P450 2B6 (CYP2B6) gene by phenobarbital-type inducers, such as 1,4

100 ched from efavirenz- to INSTI-based therapy, CYP2B6 genotype was associated with weight gain, possibl

101 PLWH in the ENCORE-1 study, irrespective of CYP2B6 genotype.

102 and not associated with pharmacokinetics or CYP2B6 genotype.

103 is study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis o

104 otal of 72% of pregnant women with extensive CYP2B6 genotypes had an efavirenz Cmin of <1 microg/mL.

105 Genotypes of CYP2B6 had an interaction with clinical efficacy of doce

106 tabolite, 2-oxo-clopidogrel, both inactivate CYP2B6 in a time- and concentration-dependent manner.

107 Interestingly, RIF-mediated induction of CYP2B6 in four -82T/C carriers was higher compared with

108 ge individual variations and inducibility of CYP2B6 in humans.

109 d antiepileptic drug, is a potent inducer of CYP2B6 in primary human hepatocytes, but does not activa

110 y to induce the prototypical CAR target gene CYP2B6 in primary human hepatocytes.

111 Our findings support a predominant role of CYP2B6 in the metabolism of BDE-47 to potentially toxic

112 ogrel inactivates human cytochrome P450 2B6 (CYP2B6) in a reconstituted system.

113 ession of Cyp2b10 (the mouse analog of human CYP2B6) in hCAR-transgenic mice.

114 formin robustly suppressed the expression of CYP2B6 induced by both indirect (phenobarbital) and dire

115 trate that, in contrast to most of the known CYP2B6 inducers, PHY is a selective activator of CAR in

116 role of RORalpha in the molecular process of CYP2B6 induction, but it also reveals the importance of

117 The CYP2B6 inhibitor 4-(4-chlorophenyl)imidazole blocked NO-

118 Retrovirus encoding a CYP2B6-IRES-P450R expression cassette was shown to induc

119 ion-deleted adenovirus engineered to express CYP2B6-IRES-P450R, induced intracellular CPA 4-hydroxyla

120 CYP2B6 is a highly inducible and polymorphic enzyme invo

121 CYP2B6 is a polymorphic cytochrome P450 isoform that con

122 CYP2B6 is a vital enzyme for the metabolic elimination o

123 CYP2B6 is also downregulated by NO in primary human hepa

124 ieved when a suitable P450 gene (e.g., human CYP2B6) is delivered in combination with NADPH-cytochrom

125 d promoter reporter assays demonstrated that CYP2B6 luciferase activity was synergistically enhanced

126 EFV/8-hydroxy-EFVmetabolic ratio was used as CYP2B6 metabolic activity index.

127 In the efavirenz arm CYP2B6 metaboliser genotype was associated with weight g

128 CYP2B6 metaboliser genotype was associated with weight g

129 munodeficiency virus type 1 (HIV-1) RNA, and CYP2B6 metaboliser genotype.

130 fat on DXA from baseline to week 48 between CYP2B6 metabolizer genotypes in the efavirenz arm, and w

131 icipants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally ha

132 by TCPOBOP generated a 10-fold induction of CYP2B6 mRNA in HepG2 cells stably expressing mouse CAR (

133 ells, we observed that all 4-NPs upregulated CYP2B6 mRNA, a relevant hallmark for CAR activation.

134 YP2B6, as some individuals completely lacked CYP2B6 mRNA.

135 down using small interfering RNAs suppressed CYP2B6 mRNAs in HPH, whereas transient expression of ROR

136 concentration decreased by 60% and 85% among CYP2B6 normal and slow/intermediate metabolizers, respec

137 variability due to genetic polymorphisms in CYP2B6, NR1I3, CYP2A6, ABCB1, ABCB5, and ABCG2.

138 the possible impact of genetic variation in CYP2B6 on response to FC chemotherapy in CLL.

139 or bupropion, abstinence was associated with CYP2B6 (OR=1.78; 95% CI: 1.27-2.50) (p<0.001).

140 iosarcoma cells retrovirally transduced with CYP2B6, or induced in wild-type 9L cells treated with ma

141 CAR preferentially induces the expression of CYP2B6 over CYP3A4 in HPHs, although endogenous expressi

142 t human enzymes demonstrated that CYP2A6 and CYP2B6 oxidized PCB 91 and PCB 132 in the meta position

143 These findings suggest that CYP2A6 and CYP2B6 play an important role in the oxidation of neurot

144 CYP2B6 played only a minor role in the metabolism of PCB

145 CYP2B6 plays an important role in the metabolism of a va

146 CYP2B6 plus P450 reductase and CYP2C18-Met plus P450 red

147 irst time, a synergistic interplay between a CYP2B6 polymorphism and PXR-mediated induction, which ma

148 Primary analyses involved 2 CYP2B6 polymorphisms (516G --> T and 983T --> C) known t

149 ted possible associations between additional CYP2B6 polymorphisms and the pharmacokinetics of nevirap

150 results suggest that clopidogrel inactivates CYP2B6 primarily through destruction of the heme, wherea

151 enhancer module in the distal region of the CYP2B6 promoter (CYP2B6-XREM) together with the PBREM me

152 ression of RORalpha in COS-1 cells activated CYP2B6 promoter activity in reporter assays.

153 rchestrated CAR-HNF4alpha interaction on the CYP2B6 promoter in human primary hepatocyte cultures.

154 lization in mouse liver, activated the human Cyp2B6 promoter in liver in vivo, and activated a report

155 nt on CYP2B6 promoter, -660/-649) within the CYP2B6 promoter in untreated or treated HPH.

156 sponse element (RORalpha response element on CYP2B6 promoter, -660/-649) within the CYP2B6 promoter i

157 binds to the distal enhancer element of the CYP2B6 promoter, which is essential in converging to its

158 requires EGR1 to enable CAR to activate the CYP2B6 promoter.

159 nd OA, respectively, to maximally induce the CYP2B6 promoter.

160 mal 24-bp (-256/-233) sequence (OARE) in the CYP2B6 promoter.

161 recruitment of PXR to the -82T-->C harboring CYP2B6 promoter; and looping the PXR-bound distal phenob

162 ding alone is not sufficient to activate the CYP2B6 promoter; the promoter requires EGR1 to enable CA

163 MM species generation, and ubiquitination of CYP2B6 protein but did not stimulate CYP2B6 degradation.

164 , PHY administration significantly increased CYP2B6 reporter gene expression, when this reporter cons

165 In primary human hepatocytes, expression of CYP2B6 reporter genes containing phenobarbital-responsiv

166 Loss-of-function polymorphisms in CYP2B6 result in higher efavirenz concentrations, which

167 e use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B, rs80210037 on chr15), and

168 increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs

169 ve evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efaviren

170 In the observational cohort (n = 61), CYP2B6 slow metabolizers had greater weight gain after s

171 In the observational cohort (N=61), CYP2B6 slow metabolizers had greater weight gain after s

172 In the clinical trials cohort (N=462), CYP2B6 slow metabolizers had lesser weight gain at week

173 In the clinical trials cohort (n = 462), CYP2B6 slow metabolizers had lesser weight gain at week

174 our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.

175 articipants with LENS would predominantly be CYP2B6 slow metabolizers.

176 , suggesting that impaired weight gain among CYP2B6 slow or intermediate metabolizers could explain t

177 al-time polymerase chain reaction assays for CYP2B6 SNPs c.516G>T and c.785A>G, which define the most

178 e metabolism and clearance of drugs that are CYP2B6 substrates.

179 ition of CAR-mediated CITCO induction of the CYP2B6 target gene.

180 However, for human CYP2B6 the relatively weak response of the PBREM to PXR

181 heme, whereas 2-oxo-clopidogrel inactivates CYP2B6 through covalent modification of Cys475.

182 volved in the regulation of CYP4F12, CYP3A4, CYP2B6, UGT1A1 and P-glycoprotein.

183 Human cytochrome P450 (P450) CYP2B6 undergoes nitric oxide (NO)-dependent proteasomal

184 apping of tryptic digests of the inactivated CYP2B6 using electrospray ionization liquid chromatograp

185 tabolite is linked to a cysteinyl residue of CYP2B6 via a disulfide bond.

186 In primary cultures of human hepatocytes, CYP2B6 was highly inducible by a number of compounds kno

187 CYP2B6 was the predominant CYP capable of forming six OH

188 ve nitrogen species cause destabilization of CYP2B6, which may act synergistically with heme nitrosyl

189 Analysis of the molecular mass of the CYP2B6 wild-type (WT) protein that had been inactivated

190 rimarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway.

191 ations predicted that tyrosine nitrations of CYP2B6 would cause significant destabilizing perturbatio

192 Furthermore, inactivation of both CYP2B6 WT and C475S by clopidogrel, but not by 2-oxo-clo

193 in the distal region of the CYP2B6 promoter (CYP2B6-XREM) together with the PBREM mediates optimal dr