ライフサイエンスコーパス: CYP2C19

1 hydroxylase (6% of the activity of wild-type CYP2C19).

2 y examines the transcriptional regulation of CYP2C19.

3 nd -1930, which are also highly conserved in CYP2C19.

4 al analogues with inhibitory potency against CYP2C19.

5 requires cytochrome P450s (CYPs), including CYP2C19.

6 and assessed for inhibitory activity against CYP2C19.

7 iting various hepatic CYP450 enzymes, mainly CYP2C19.

8 ->T genotype and reduced-function alleles of CYP2C19.

9 ity was associated with the gain-of-function CYP2C19*17 allele (adjusted HR for *1/*17 versus *1/*1:

10 R for hetero- and homozygote carriers of the CYP2C19*17 allele were 1.02 (CI 0.71-1.46) and 0.57 (CI

11 ficantly more common among black carriers of CYP2C19*17 or CYP1A2*1C.

12 patients homozygous for CYP2B6*5 (n = 3) or CYP2C19*2 (n = 4) had a higher probability of reaching E

13 clopidogrel response is not explained by the CYP2C19*2 allele (the most frequent loss-of-function all

14 ong whites, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mort

15 iable external factors, the influence of the CYP2C19*2 allele is intrinsically constant.

16 For the CYP2C19*2 allele, the HR was 1.05 (CI 0.78-1.42) and 0.7

17 The relation between CYP2C19*2 genotype and platelet aggregation was replicat

18 y were extended by examining the relation of CYP2C19*2 genotype to platelet function and cardiovascul

19 CYP2C19*2 genotype was associated with diminished platel

20 o were either heterozygous or homozygous for CYP2C19*2 had a significantly lower risk of developing p

21 Independently, in post hoc analyses, CYP2C19*2 has been associated with worse clinical outcom

22 nance dose of clopidogrel to 225 mg daily in CYP2C19*2 heterozygotes achieved levels of platelet reac

23 With 75 mg daily, CYP2C19*2 heterozygotes had significantly higher on-trea

24 225 mg daily, reduced platelet reactivity in CYP2C19*2 heterozygotes to levels achieved with standard

25 Whereas 52% of CYP2C19*2 heterozygotes were nonresponders (>/=230 PRU)

26 Among CYP2C19*2 heterozygotes, doses up to 300 mg daily signif

27 75-mg dose in noncarriers; in contrast, for CYP2C19*2 homozygotes, doses as high as 300 mg daily did

28 In CYP2C19*2 homozygotes, even with 300 mg daily of clopido

29 In total, 247 noncarriers of a CYP2C19*2 loss-of-function allele were to receive 75 and

30 clopidogrel and prasugrel in the 18 (56.3%) CYP2C19*2 noncarriers (HTPR in 12.5% versus 0, P=0.274),

31 gh-dose clopidogrel can address HTPR only in CYP2C19*2 noncarriers.

32 CYP2C19*2 or *19 alleles did not influence DFS.

33 notypes and enrolled 103 patients who lacked CYP2C19*2 or *3 loss-of-function allele to minimize the

34 ompared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred pre

35 Furthermore, patients with the CYP2C19*2 variant were more likely (20.9% vs 10.0%) to h

36 as in strong linkage disequilibrium with the CYP2C19*2 variant, and was associated with diminished cl

37 CYP2C19*2 was significantly associated with OTR at 12 to

38 frequencies of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0

39 d with the polymorphisms CYP2B6 516G-->T and CYP2C19 681G-->A, respectively.

40 failure was associated with the polymorphism CYP2C19 681G-->A.

41 essential for the stimulation of CYP2E1 and CYP2C19 activities and that the phospholipid composition

42 vention, carriage of even 1 reduced-function CYP2C19 allele appears to be associated with a significa

43 at 30 days attributable to reduced-function CYP2C19 allele carriage was 5.2% in the patients randoml

44 likely to intensify antiplatelet therapy in CYP2C19 allele carriers, but only 20% of poor metabolize

45 clopidogrel, carriers of a reduced-function CYP2C19 allele had significantly lower levels of the act

46 re noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19

47 t on factors that decrease (reduced-function CYP2C19 allele; omeprazole) or increase (cigarette smoki

48 th clopidogrel, carriers of reduced-function CYP2C19 alleles have significantly lower levels of activ

49 Carriers of 1 and 2 reduced-function CYP2C19 alleles were significantly more likely to displa

50 5% CI, 1.24-2.50; P = .002) reduced-function CYP2C19 alleles, as compared with noncarriers.

51 2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles.

52 throughput sequencing to assay mutations in CYP2C19 and ABCB1, the two genes genetically linked to r

53 uble mutation stimulated these activities of CYP2C19 and CYP2E1 equivalent to wild-type b(5).

54 trate recognition sites (SRSs) with those of CYP2C19 and mutating individual residues by site-directe

55 ) enhances the activities of CYP3A4, CYP2A6, CYP2C19, and CYP17A1 but not that of CYP2E1 or CYP2D6, s

56 Lower levels of CYP2C18, CYP2C19, and CYP3A5 were also detected while CYP1A2, 2A6

57 Cytochrome P450 (CYP)2C9 and CYP2C19 are important human enzymes that metabolize ther

58 rcutaneous intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of the popul

59 Testing for mutations in CYP2C19, as recommended by the FDA, only correctly predi

60 such as rifampicin and dexamethasone induce CYP2C19 both in vivo in humans and in vitro in human hep

61 tion activity with a K(M) similar to that of CYP2C19 but a 3-fold lower K(cat).

62 CYP2C19, but not PON1 or ABCB1, is a significant determi

63 65G double mutation also failed to stimulate CYP2C19-catalyzed (S)-mephenytoin 4-hydroxylation, where

64 and was selective in regard to inhibition of CYP2C19-catalyzed (S)-mephenytoin hydroxylation in human

65 suggest that these receptors may up-regulate CYP2C19 constitutively and possibly its response to drug

66 tion allele for any of the CYP genes tested (CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP1A2).

67 hisms on chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with dimin

68 Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizi

69 epatic CYP enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial steroidogeni

70 on of alpha-thujone by human CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 occurs with up to 80

71 tional P450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5).

72 iated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxid

73 Polymorphisms in CYP2B6, CYP2C19, CYP3A4, CYP3A5, and MDR1 were characterized.

74 or control of known disease, polymorphisms (CYP2C19, CYP3A5, ABCB1, PON1), noncompliance, co-medicat

75 Likewise, Bzbr-based CoMFA models of CYP2C19 demonstrated no clear preference for any one lig

76 (n = 160, age 18 to 55 years, homozygous for CYP2C19 extensive metabolizer genotype, confined, standa

77 ts (n = 160; ages 20 to 53 years; homozygous CYP2C19 extensive metabolizer genotype; no nicotine for

78 o acids determining the specificity of human CYP2C19 for S-mephenytoin 4'-hydroxylation, we construct

79 Certain alleles of the CYP2C19 gene are associated with higher platelet reactiv

80 Variants in the CYP2C19 gene influence the pharmacologic and clinical re

81 ytes showed induction of both the CYP2C9 and CYP2C19 genes by tert-butylhydroquinone (tBHQ).

82 ent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of

83 Our findings do not support routine CYP2C19 genetic testing in this population.

84 We sought to assess the impact of CYP2C19 genetic testing on prescribing patterns for anti

85 ith HTPR and explore the interaction between CYP2C19 genotype and both drugs.

86 s (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and pla

87 However, the relationship of CYP2C19 genotype and outcomes in medically managed patie

88 CYP2C19 genotype data was available for 2 423 patients a

89 Meta-analysis of the CYP2C19 genotype effect was stratified by the predominan

90 This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with A

91 identified by platelet function testing, the CYP2C19 genotype provides limited incremental informatio

92 in breast cancer patients and, consequently, CYP2C19 genotype status should not be included in clinic

93 bolite levels, cytochrome P450 1A2 activity, CYP2C19 genotype, and safety parameters were determined.

94 est its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the

95 ave been proposed to influence the effect of CYP2C19 genotype.

96 ed by therapy with prasugrel irrespective of CYP2C19 genotype.

97 ABCB1 3435C-->T and CYP2C19 genotypes were significant, independent predicto

98 Clinical follow-up (until 3 months) and CYP2C19 genotyping was performed in all patients.

99 ts were identified, and 499 (8.3%) underwent CYP2C19 genotyping, of whom 146 (30%) were found to have

100 l who have >/=1 loss of function alleles for CYP2C19 have an increased risk for adverse cardiovascula

101 mpounds were docked into a homology model of CYP2C19 in an effort to understand the enzyme-ligand int

102 bolites induces the expression of CYP2C9 and CYP2C19 in human hepatocytes.

103 ssing SRSs 1--4 was active (30% of wild-type CYP2C19), indicating that multiple regions are necessary

104 The data was used to build a CYP2C19 inhibition pharmacophore model for the series.

105 nzbromarone (Bzbr) to create the most potent CYP2C19 inhibitor ever reported.

106 CYP2C19 is an important human drug-metabolizing enzyme t

107 ve been intensively studied, but the role of CYP2C19 is less elucidated, and we studied the associati

108 CYP2C19 is selective for the 4'-hydroxylation of S-mephe

109 Upon identifying inhibitors of CYP2C19, ligand-based design shifted to attenuating the

110 The reported association between CYP2C19 LoF allele carriage and major cardiovascular out

111 s were identified in secondary analyses of 2 CYP2C19 LoF alleles, stent thrombosis outcomes, and stud

112 nce given that over 50% of Asians carry >/=1 CYP2C19 LoF alleles.

113 The association between carriage of >/=1 CYP2C19 loss-of-function (LoF) allele and major cardiova

114 to sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele carriers.

115 hemical inhibitor (tranylcypromine) for this CYP2C19-mediated reaction.

116 There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary c

117 CYP2C19 metabolizer status is not associated with the co

118 ssion with hCAR also up-regulated endogenous CYP2C19 mRNA content in HepG2 cells.

119 morphism by itself and alongside variants in CYP2C19 on cardiovascular outcomes in patients treated w

120 e to support a clinically meaningful role of CYP2C19 polymorphisms and response to tamoxifen in breas

121 t reactivity including cytochrome P450 2C19 (CYP2C19) polymorphisms, age, body mass index, diabetes,

122 However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopi

123 ceptor binding sites (CAR/PXR and GR) in the CYP2C19 promoter and to suggest that these receptors may

124 Dexamethasone activated the -2.7-kb CYP2C19 promoter constructs in HepG2 cells only in the p

125 in HepG2 cells up-regulated transcription of CYP2C19 promoter constructs, whereas mutation of the -18

126 mCAR-mediated constitutive activation of the CYP2C19 promoter in HepG2 cells, whereas the potent mCAR

127 Analysis of the CYP2C19 promoter revealed a single constitutive androsta

128 d with clopidogrel, carriers of at least one CYP2C19 reduced-function allele (approximately 30% of th

129 patients taking clopidogrel who were either CYP2C19 reduced-function allele carriers, ABCB1 3435 TT

130 nd 2 (HR, 3.97; 95% CI, 1.75-9.02; P = .001) CYP2C19 reduced-function alleles, as compared with nonca

131 etabolized by cytochrome P-450 (CYP) 2B6 and CYP2C19, respectively, with some involvement by CYP3A.

132 patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, seve

133 lizing enzymes GSTT1, GSTM1, CYP1A1, CYP2D6, CYP2C19, SULT1A1, and NQO1 were previously determined fo

134 rvention prescribed clopidogrel were offered CYP2C19 testing.

135 explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformatio

136 hydroxylation reaction as performed by human CYP2C19, the major human omeprazole-metabolizing P450 en

137 Though CYP2C19 was known to prefer neutral substrates, the exte

138 were also found in the 3'-UTRs of CYP2C9 and CYP2C19, which suggested that the same miRNAs could regu

139 agrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiv

140 atures enabling analogues of Bzbr to bind to CYP2C19 with high affinity are low acidity (high pK(a) o