ライフサイエンスコーパス: CYP2B6

1 mediates optimal drug-induced expression of CYP2B6.

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

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

4 n of the active metabolite of clopidogrel to CYP2B6.

5 tion could affect drug-mediated induction of CYP2B6.

6 tocytes, is responsible for PHY induction of CYP2B6.

7 trations associated with potent induction of CYP2B6.

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

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

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

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

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

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

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

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

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

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

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

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

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

21 CYP2B6 516G>T was independently associated with efaviren

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

23 5; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), M

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

55 2C9, 2D6, and 2E1) examined, only CYP1A2 and CYP2B6 could catalyze ortho hydroxylation of [o-3H]metho

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

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

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

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

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

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

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

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

64 The CYP2B6 enzyme metabolizes commonly used therapeutics and

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

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

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

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

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

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

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

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

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

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

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

76 the transcriptional regulation of the human CYP2B6 gene.

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

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

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

80 and not associated with pharmacokinetics or CYP2B6 genotype.

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

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

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

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

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

86 ge individual variations and inducibility of CYP2B6 in humans.

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

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

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

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

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

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

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

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

95 CYP2B6 is a highly inducible and polymorphic enzyme invo

96 CYP2B6 is a polymorphic cytochrome P450 isoform that con

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

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

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

100 YP2B6, as some individuals completely lacked CYP2B6 mRNA.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

131 CYP2B6 was the predominant CYP capable of forming six OH

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

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

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