ライフサイエンスコーパス: CYP2C9

1 tic regulation of human cytochrome P450 2C9 (CYP2C9).

2 oxicity profile except for the inhibition of CYP2C9.

3 ologic target of warfarin, VKORC1, than with CYP2C9.

4 andidate polymorphisms detected in COX-1 and CYP2C9.

5 cur in individuals with this variant form of CYP2C9.

6 urbiprofen and dapsone in the active site of CYP2C9.

7 tabolism of negatively charged substrates of CYP2C9.

8 correlated inversely with the expression of CYP2C9.

9 loop region between the B' and C helices of CYP2C9.

10 C9, and 3A5 as well as dapsone metabolism by CYP2C9.

11 nd human), and 32 did not inhibit CYP3A4 nor CYP2C9.

12 ional activation of a highly inducible gene, CYP2C9.

13 rm covalent adducts with CYP2E1, CYP3A4, and CYP2C9.

14 are essential for tBHQ-induced expression of CYP2C9.

15 f the major drug-metabolizing P450 isoforms, CYP2C9.

16 important role in controlling selectivity in CYP2C9.

17 farin therapy, we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haplotypes (designated A

18 s differed less than K(m) values between the CYP2C9*1 and CYP2C9*5 proteins.

19 2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single aminoacid substitution in each case

20 increase the K(m) value relative to that of CYP2C9*1 for all three substrates: 12-fold higher for (S

21 atio of V(max)/K(m), ranged from 8 to 18% of CYP2C9*1 values.

22 which there are four known allelic variants; CYP2C9*1, CYP2C9*2, CYP2C9*3, and CYP2C9*4.

23 studies using the purified wild-type protein CYP2C9*1; the Ile359Leu variant, CYP2C9*3; and the Asp36

24 Although benzbromarone inhibited CYP2C9.1 activity as expected, CYP2C9.3-mediated flurbip

25 enzyme to the high spin state was similar in CYP2C9.1 and CYP2C9.2, but lower in CYP2C9.3.

26 Uncoupling in CYP2C9.1 and CYP2C9.3 was primarily to H(2)O(2).

27 ect on flurbiprofen-binding affinity in both CYP2C9.1 and CYP2C9.3.

28 .3 not only reduces metabolism compared with CYP2C9.1 but can also dramatically alter inhibitor effec

29 Coupling was greatest in the CYP2C9.1 enzyme, followed by CYP2C9.2, and then CYP2C9.3

30 iprofen protons from the heme iron of either CYP2C9.1 or CYP2C9.3 in the presence of benzbromarone co

31 r, benzbromarone, was studied with regard to CYP2C9.1- and CYP2C9.3-mediated flurbiprofen metabolism

32 CYP1A2-15q22-ter, CYP1B1-2p21, CYP2C8-10q23, CYP2C9-10q24, and MAOA-Xp11.4 regions as significantly a

33 he effects of plumbagin on CYP1A2, CYP2B1/6, CYP2C9/11, CYP2D1/6, CYP2E1 and CYP3A2/4 activities in h

34 enotyped for VKORC1 (-1639G > A; rs9923231), CYP2C9 (*2 and *3 alleles; rs1799853 and rs1057910), and

35 Buccal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1C1173T with a rapid as

36 CYP2C9( *)2 (p.R144C), CYP2C9( *)3 (p.I359L), and the VK

37 The "sensitive"CYP2C9( *)2 and ( *)3 alleles had significantly higher f

38 would be misclassified when only genotyping CYP2C9( *)2, ( *)3, and VKORC1 g.-1639G-->A, underscorin

39 J individuals have at least one "sensitive" (CYP2C9( *)2, ( *)3, VKORC1 g.-1639G-->A) or "resistant"

40 two of which included the g.3608C>T (R144C) CYP2C9(*)2 and two the g.42614A>C (I359L) CYP2C9(*)3 SNP

41 sic kinetics substrate (S)-naproxen, and the CYP2C9*2 (R144C) and CYP2C9*3 (I359L) variants are assoc

42 We examined the influence of CYP2C9*2 (R144C) and CYP2C9*3 (I359L) variants on dose-r

43 significant risk reduction among those with CYP2C9*2 (RR, 0.83; 95% CI: 0.57-1.21) or wild-type (RR,

44 Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis.

45 Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1

46 We identified individuals with CYP2C9*2 and CYP2C9*3 genotypes (>or=1 variant allele) i

47 The results of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated with

48 with reduced activity have been identified, CYP2C9*2 and CYP2C9*3.

49 in dose in African Americans, independent of CYP2C9*2 and CYP2C9*3.

50 G-->A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3.

51 P2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and

52 t warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (-38% and -17% per allele), estimated

53 CYP2C9*2 was associated with a lower dose only among Eur

54 D], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F

55 Among 1660 patients, 21% were CYP2C9*2, and 12% were CYP2C9*3 genotypes.

56 of the variant alleles CYP2B6*5, CYP2C19*2, CYP2C9*2, and CYP3A5*3 were 12.1%, 25.0%, 4.0%, and 75.8

57 e are four known allelic variants; CYP2C9*1, CYP2C9*2, CYP2C9*3, and CYP2C9*4.

58 the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.

59 Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G-->A) was performe

60 les that affect appropriate warfarin dosage (CYP2C9*2, CYP2C9*3, and VKORC1 1173C > T).

61 e-guided dosing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1 versus standard warfar

62 In contrast, CYP2C9.2 uncoupled to excess water preferentially.

63 greatest in the CYP2C9.1 enzyme, followed by CYP2C9.2, and then CYP2C9.3.

64 high spin state was similar in CYP2C9.1 and CYP2C9.2, but lower in CYP2C9.3.

65 A panel of CYP2C9/2C19 chimeric proteins was constructed in order t

66 cal swab DNA was genotyped for CYP2C9 *2 and CYP2C9 *3 and VKORC1C1173T with a rapid assay.

67 CYP2C9( *)2 (p.R144C), CYP2C9( *)3 (p.I359L), and the VKORC1 promoter (g.-1639G

68 C) CYP2C9(*)2 and two the g.42614A>C (I359L) CYP2C9(*)3 SNPs.

69 e (S)-naproxen, and the CYP2C9*2 (R144C) and CYP2C9*3 (I359L) variants are associated with lower rate

70 amined the influence of CYP2C9*2 (R144C) and CYP2C9*3 (I359L) variants on dose-related response or to

71 Genotyping for the CYP2C9*2 and CYP2C9*3 alleles was done by PCR analysis.

72 t rise), first warfarin dose (+7% per 1 mg), CYP2C9*3 and CYP2C9*2 genotype (-38% and -17% per allele

73 s were significant in most ethnic groups for CYP2C9*3 and stable dose (mutant types requiring between

74 uenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2

75 Two known allelic variants CYP2C9*2 and CYP2C9*3 differ from the wild type CYP2C9*1 by a single

76 Ibuprofen's clearance varies with CYP2C9*3 genotype.

77 We identified individuals with CYP2C9*2 and CYP2C9*3 genotypes (>or=1 variant allele) in the Adenoma

78 he low-dose, was observed only in those with CYP2C9*3 genotypes (RR, 0.51; 95% CI: 0.30-0.87).

79 60 patients, 21% were CYP2C9*2, and 12% were CYP2C9*3 genotypes.

80 s of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated with an increased

81 The corresponding ratio for CYP2C9*3 was 4 to 13%.

82 CYP2C9 (rs1057910 CYP2C9*3) and rs4917639) was associated with dose at mod

83 nfined to individuals with slow metabolizer (CYP2C9*3) genotypes.

84 known allelic variants; CYP2C9*1, CYP2C9*2, CYP2C9*3, and CYP2C9*4.

85 ing polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M.

86 Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G-->A) was performed with the

87 ffect appropriate warfarin dosage (CYP2C9*2, CYP2C9*3, and VKORC1 1173C > T).

88 osing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1 versus standard warfarin inducti

89 activity have been identified, CYP2C9*2 and CYP2C9*3.

90 rican Americans, independent of CYP2C9*2 and CYP2C9*3.

91 ed by the composite genotype of CYP2C9*2 and CYP2C9*3.

92 ype protein CYP2C9*1; the Ile359Leu variant, CYP2C9*3; and the Asp360Glu variant, CYP2C9*5 were carri

93 ons from the heme iron of either CYP2C9.1 or CYP2C9.3 in the presence of benzbromarone compared with

94 , the I359L amino acid substitution found in CYP2C9.3 not only reduces metabolism compared with CYP2C

95 The CYP2C9.3 variant exhibits marked decreases in substrate

96 Uncoupling in CYP2C9.1 and CYP2C9.3 was primarily to H(2)O(2).

97 one inhibited CYP2C9.1 activity as expected, CYP2C9.3-mediated flurbiprofen 4'-hydroxylation was acti

98 ne, was studied with regard to CYP2C9.1- and CYP2C9.3-mediated flurbiprofen metabolism to evaluate wh

99 milar in CYP2C9.1 and CYP2C9.2, but lower in CYP2C9.3.

100 2C9.1 enzyme, followed by CYP2C9.2, and then CYP2C9.3.

101 profen-binding affinity in both CYP2C9.1 and CYP2C9.3.

102 variants; CYP2C9*1, CYP2C9*2, CYP2C9*3, and CYP2C9*4.

103 e in vitro data suggest that carriers of the CYP2C9*5 allele would eliminate CYP2C9 substrates at slo

104 roximately 3% of this population carries the CYP2C9*5 allele.

105 ss than K(m) values between the CYP2C9*1 and CYP2C9*5 proteins.

106 The CYP2C9*5 variant was found to be expressed only in Afric

107 ariant, CYP2C9*3; and the Asp360Glu variant, CYP2C9*5 were carried out using (S)-warfarin, diclofenac

108 In vitro intrinsic clearances for CYP2C9*5, calculated as the ratio of V(max)/K(m), ranged

109 the identification of a new CYP2C9 variant, CYP2C9*5.

110 l serum, MYC induced increased expression of CYP2C9, a gene product well known to be associated with

111 e determinants of specificity for cytochrome CYP2C9, a novel library of benzbromarone (bzbr) inhibito

112 amino acids in the substrate specificity of CYP2C9, a series of mutants were constructed and analyze

113 had anti-CYP3A4 antibodies, and 10 had anti-CYP2C9 Abs.

114 oxylation of diclofenac, suggesting that the CYP2C9 active site favors cooperative binding of nonster

115 al simulations reveal CBN's stability at the CYP2C9 active site, driving hydroxy metabolite formation

116 00-fold increase in the Ki for inhibition of CYP2C9 activity by sulfaphenazole.

117 Finally, it is also shown that the CPR(ox)/CYP2C9 affinity depends on the nature of the ligand, bei

118 able data, 58 (31.4%) had at least 1 variant CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1)

119 The conductivity measurements were made on CYP2C9 alone and with bound substrates, a bound substrat

120 Samples contained 0.014 microM CYP2C9 and 145 microM flurbiprofen in the presence and a

121 man hepatocytes showed induction of both the CYP2C9 and CYP2C19 genes by tert-butylhydroquinone (tBHQ

122 cs and metabolites induces the expression of CYP2C9 and CYP2C19 in human hepatocytes.

123 MRE motifs were also found in the 3'-UTRs of CYP2C9 and CYP2C19, which suggested that the same miRNAs

124 d cDNA-expressed human P450 isozyme studies, CYP2C9 and CYP3A4/5 seemed to be the major P450 isoforms

125 e, screened a set of drugs for inhibition of CYP2C9 and determined the Ki values for inhibitors.

126 di Jewish (SJ) individuals, we genotyped six CYP2C9 and eight VKORC1 alleles by using the Tag-It Muta

127 o phenotypes, while some pharmacogenes (i.e. CYP2C9 and SLCO1B1) are modestly associated with persist

128 erase reporter gene containing the 3'-UTR of CYP2C9 and the endogenous expression of CYP2C9 were supp

129 CYP2C9 and UGT1A6 genotypes were determined for 474 aden

130 Warfarin-dosing algorithms incorporating CYP2C9 and VKORC1 -1639G>A improve dose prediction compa

131 To compare the CYP2C9 and VKORC1 allele and genotype frequencies among

132 Although the polymorphisms in CYP2C9 and VKORC1 explain a significant proportion of th

133 Prospective studies that incorporate both CYP2C9 and VKORC1 genes and environmental factors in war

134 are unlikely to be discovered outside of the CYP2C9 and VKORC1 genes.

135 Thus, much of the information provided by CYP2C9 and VKORC1 genotypes during warfarin initiation i

136 CYP2C9 and VKORC1 genotypes identify patients who are mo

137 ided dose adjustments, we determined whether CYP2C9 and VKORC1 genotypes were associated with early m

138 A rapid method provided same-day CYP2C9 and VKORC1 genotyping.

139 Variants in CYP2C9 and VKORC1 have been associated with acenocoumaro

140 Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin do

141 lysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumar

142 Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin

143 cluded clinical variables and genotyping for CYP2C9 and VKORC1 with a dosing algorithm that included

144 cokinetic and pharmacodynamic genes, such as CYP2C9 and VKORC1, do not fully explain the dose variabi

145 Two genes, CYP2C9 and VKORC1, have been associated with this variab

146 Based on combined polymorphisms in CYP2C9 and VKORC1, we established a clinical classificat

147 netic analysis and genotyped for variants in CYP2C9 and VKORC1.

148 e defines unanticipated interactions between CYP2C9 and warfarin, and reveals a new binding pocket.

149 de polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKOR) genes hav

150 metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin,

151 al enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms with reduc

152 13 in the hydrophobic binding of warfarin to CYP2C9, and are consistent with pi-stacking to F114 for

153 NOS1AP, SCN5A, IGFBP3, CYP2C9, and CAV1 showed evidence of differential allelic

154 rug induction studies, where CYP3A4, CYP1A2, CYP2C9, and CYP2C19 inductions were achieved following r

155 sporters: namely, cytochrome P450 (CYP) 3A4, CYP2C9, and CYP2D6, organic anion transporting polypepti

156 other AA-oxidizing P450s, including CYP2C8, CYP2C9, and CYP2E1, were not expressed.

157 increases in immunoreactive CYP2B6, CYP2C8, CYP2C9, and CYP3A4, all previously shown to catalyze oxa

158 height, genetic polymorphisms in VKORC1 and CYP2C9, and indication for warfarin.

159 In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dos

160 VKORC1 and CYP2C9 are important contributors to warfarin dose varia

161 te of diclofenac interacts strongly with the CYP2C9 Arg108 side chain in the transition state for for

162 elevated thermostability relative to that of CYP2C9, as well as a UV-visible absorbance spectrum that

163 ibe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coa

164 Specific inhibition of CYP2C9 by small interfering RNA was shown to partially i

165 ate the molecular basis of the activation of CYP2C9-catalyzed S-flurbiprofen 4'-hydroxylation and S-n

166 CYP2C9 catalyzes the demethylation of the biphasic kinet

167 d characterizing genetic variants within the CYP2C9 coding region.

168 It is shown that CPR(ox)/CYP2C9 complexes have a much higher dissociation constan

169 determine the dissociation constants of CPR/CYP2C9 complexes in a lipid bilayer membrane for the fir

170 tion constant than CPR(2-)/CYP2C9 or CPR(4-)/CYP2C9 complexes, and a model is presented to account fo

171 study the range of energetically accessible CYP2C9 conformations.

172 onstructed chimeras by replacing portions of CYP2C9 containing various proposed substrate recognition

173 The promoter region of CYP2C9 contains two putative AP-1 sites (TGAGTCA) at pos

174 lizing-enzyme genes (such as CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2E1 and UGT1A4) in THLE-2 cell microa

175 le for any of the CYP genes tested (CYP2C19, CYP2C9, CYP2B6, CYP3A5, and CYP1A2).

176 Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-me

177 nel of hepatic CYP enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial ster

178 oxidation of alpha-thujone by human CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 occurs with

179 of additional P450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5).

180 ne-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for

181 chromosome 10q24 within the CYP2C18-CYP2C19-CYP2C9-CYP2C8 cluster were associated with diminished cl

182 e most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.

183 in was not only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-compet

184 women who were homozygous wild-type for the CYP2C9, CYP2E1, or GSTM3 polymorphisms, women carrying 1

185 hanism, MGd is also an in vitro inhibitor of CYP2C9, CYP3A4, and CYP4A1.

186 We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7 reduced functio

187 ontribution of nongenetic factors and VKORC1/CYP2C9/CYP4F2 genotypes on warfarin (n = 83) or fluindio

188 abolism by CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme kinetics sugges

189 knockdown of CYP2C55, the homologous gene of CYP2C9, demonstrated viability rescue to light-induced c

190 CYP2C9 encodes a cytochrome P450 enzyme responsible for

191 an PPARalpha down-regulates endothelial cell CYP2C9 epoxygenase expression and blunts proliferation a

192 s tumor angiogenesis and growth, and (c) the CYP2C9 epoxygenase is expressed in the vasculature of hu

193 n-Hodgkin lymphoma was found for carriers of CYP2C9 Ex3-52C>T TT/CT genotypes (odds ratio (OR) = 2.9,

194 microRNA hsa-miR-128-3p in the regulation of CYP2C9 expression and translation.

195 e X receptor (PXR) and subsequent CYP3A4 and CYP2C9 expression in hPSC-derived and isolated fetal hep

196 tigate the molecular mechanisms that control CYP2C9 expression, we applied integrative approaches inc

197 contribute to interindividual differences in CYP2C9 expression.

198 ote, 11.3% of AJ individuals predicted to be CYP2C9 extensive metabolizers and 8.7% of those predicte

199 statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CYP2C9), for which sufficient data exists for statistica

200 chanism of the synergistic activation of the CYP2C9 gene by CAR and HNF4alpha.

201 romoter and the synergistic induction of the CYP2C9 gene by CAR-HNF4alpha.

202 Variants in the cytochrome P450 2C9 (CYP2C9) gene are associated with impaired metabolism of

203 plex 1 (VKORC1) and the cytochrome P450 2C9 (CYP2C9) genes.

204 Genetic polymorphisms in VKORC1 and CYP2C9, genes controlling vitamin K(1) (VK1) epoxide red

205 f warfarin, but a direct association between CYP2C9 genotype and anticoagulation status or bleeding r

206 Both the CYP2C9 genotype and VKORC1 haplotype had a significant i

207 In contrast, the CYP2C9 genotype was not a significant predictor of the t

208 ients starting warfarin therapy, we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haploty

209 nternational normalized ratio and VKORC1 and CYP2C9 genotypes were the main determinants of warfarin

210 CYP2C9 genotyping may identify a subgroup of patients wh

211 ath, whereas stable expression of functional CYP2C9-GFP fusion protein further exacerbated light-indu

212 on of S-mephenytoin while the highly similar CYP2C9 has little activity toward this substrate.

213 We have used analogues of the prototypical CYP2C9 heteroactivator dapsone to validate a simple dock

214 ng compounds identified was verified to be a CYP2C9 heteroactivator in vitro, and it possessed activi

215 A crystal structure of CYP2C9 in complex with a TCA1 analog revealed the simila

216 inversely correlated with the expression of CYP2C9 in HCC tumor tissues.

217 for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor

218 The expression of CYP2C9 in the liver also resulted in viable animals acti

219 n of flurbiprofen closer to the heme iron of CYP2C9 in the presence of dapsone may play a role in act

220 ablish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a d

221 of the R108H mutant of cytochrome P450 2C9 (CYP2C9), including elevated thermostability relative to

222 The resulting series is devoid of the CYP2C9 inhibition liability of MRK-560.

223 inetic properties, including PXR activation, CYP2C9 inhibition, and CYP3A4 TDI, several compounds wer

224 n solubility, selectivity over Na(V)1.5, and CYP2C9 inhibition.

225 e P450 2C8 (CYP2C8) and cytochrome P450 2C9 (CYP2C9) inhibition, and a good mouse pharmacokinetics (P

226 e this possibility, the effect of the potent CYP2C9 inhibitor, benzbromarone, was studied with regard

227 dicts the Ki values for cytochrome P450 2C9 (CYP2C9) inhibitors.

228 onstrating that the reduced forms of CPR and CYP2C9 interact differently with the biomimetic ER and m

229 emonstrate the transient nature of these CPR-CYP2C9 interactions, and the measured Kd values are high

230 CYP2C9 is a polymorphic gene for which there are four kn

231 CYP2C9 is a significant P450 protein responsible for dru

232 CYP2C9 is an important enzyme that metabolizes both comm

233 ve suggested that coumarin ligand binding to CYP2C9 is dictated by electrostatic and pi-stacking inte

234 CYP2C9 is important for the metabolism of many exogenous

235 trated that the binding of flurbiprofen with CYP2C9 is increased (decrease in K(S)) by the presence o

236 Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of

237 between the open and closed conformations of CYP2C9 is presented, which helps to explain the enzyme's

238 The cytochrome P450 CYP2C9 is responsible for the metabolism of S-warfarin.

239 to reduce serum shift and both CYPCYP2C8 and CYP2C9 liabilities, while improving PK and maintaining e

240 Haplotype variants were introduced into a CYP2C9/luciferase reporter plasmid using site-directed m

241 discovered binding pocket also suggests that CYP2C9 may simultaneously accommodate multiple ligands d

242 The binding mode of warfarin suggests that CYP2C9 may undergo an allosteric mechanism during its fu

243 Cytochrome P450 2C9 (CYP2C9)-mediated flurbiprofen 4'-hydroxylation is activa

244 height for electron transfer and the ease of CYP2C9-mediated metabolism of the bound substrates, thou

245 CYP2C9 metabolizes a wide range of drugs, many of which

246 scently labeled CPR and cytochrome P450 2C9 (CYP2C9) molecules in which stochastic analysis was used

247 o studies showed that the B-C loop region of CYP2C9 moves away from the heme to a position resembling

248 (hCAR) into HepG2 cells results in increased CYP2C9 mRNA content.

249 chromatin state that reflected increases in CYP2C9 mRNA.

250 For CYP2C9, no clear trend between activity and physicochemi

251 CYP2C9, one of the most abundant and important DMEs, is

252 ch higher dissociation constant than CPR(2-)/CYP2C9 or CPR(4-)/CYP2C9 complexes, and a model is prese

253 ning sulfaphenazole (a specific inhibitor of CYP2C9) or troleandomycin (a specific CYP3A inhibitor) d

254 ored during coincubation of (S)-naproxen and CYP2C9 over a range of P450 reductase concentrations.

255 After inclusion of week 1 INRs, CYP2C9 (P = .08) and VKORC1 (P = .30) were not associate

256 SNP adjusted analysis, nine SNPs in the XPC, CYP2C9, PAX4, MTRR, and GAN genes were associated with c

257 es is likely to contribute to differences in CYP2C9 phenotype both within and among different populat

258 We have studied the effect of CYP2C9 polymorphism on the in-vivo warfarin dose require

259 NF4alpha and distal CAR binding sites of the CYP2C9 promoter and provides the basis for the recruitme

260 abrogated the synergistic activation of the CYP2C9 promoter and the synergistic induction of the CYP

261 inducibility to the proximal -2145 bp of the CYP2C9 promoter in luciferase assays.

262 The CYP2C9 promoter is activated by ectopic expression of cF

263 MED25 is recruited to the CYP2C9 promoter through association with liver-enriched

264 enobiotic-sensing receptor) up-regulates the CYP2C9 promoter through binding to a distal site, wherea

265 w CAR/PXR binding site was identified in the CYP2C9 promoter, and this site seems to constitutively r

266 confirmed the formation of a DNA loop in the CYP2C9 promoter, possibly allowing interaction between c

267 proximal AP-1 sites together to activate the CYP2C9 promoter.

268 CYP3A4, CYP2C8, and CYP2C9 protein levels were also increased by exposure of

269 hy and UV-visible absorbance spectroscopy of CYP2C9 R108H monomers demonstrated that nitrogen ligatio

270 Pulsed electron paramagnetic resonance of CYP2C9 R108H monomers showed that a histidine is most li

271 e study helped to elucidate the mechanism of CYP2C9 regulation by hsa-miR-128-3p, and the inverse ass

272 e data suggest that genetic variation within CYP2C9 regulatory sequences is likely to contribute to d

273 CYP2C9 (rs1057910 CYP2C9*3) and rs4917639) was associate

274 To elucidate the importance of CYP2C9's active site phenylalanines on substrate binding

275 TPMT), clopidogrel (CYP2C19), statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CYP2C9), for which sufficie

276 d a corresponding humanized model expressing CYP2C9 specifically in the liver.

277 riers of the CYP2C9*5 allele would eliminate CYP2C9 substrates at slower rates relative to persons ex

278 he metabolism and disposition of a number of CYP2C9 substrates.

279 hey establish a pharmacophore for binding to CYP2C9 that can be tested with site-directed mutagenesis

280 ived from a C1080G transversion in exon 7 of CYP2C9 that leads to an Asp360Glu substitution in the en

281 mponents of the proteins required to convert CYP2C9 to an S-mephenytoin 4'-hydroxylase (6% of the act

282 n hsa-miR-128-3p and its cognate target, the CYP2C9 transcript.

283 te and JunD at the proximal site to activate CYP2C9 transcription in response to electrophiles.

284 problem, approximately 10,000 base pairs of CYP2C9 upstream information were resequenced using 24 DN

285 pproach to measure the catalytic activity of CYP2C9 using the high-throughput technique self-assemble

286 was absent in aspirin users who carried the CYP2C9 variant alleles (OR, 0.88; 95% CI, 0.51-1.53) or

287 n that there is a strong association between CYP2C9 variant alleles and low warfarin dose requirement

288 warfarin dose requirement having one or more CYP2C9 variant alleles compared with the normal populati

289 es, resulting in the identification of a new CYP2C9 variant, CYP2C9*5.

290 izing up to 15% of small molecule drugs, and CYP2C9 variants can alter the safety and efficacy of the

291 Screening for CYP2C9 variants may allow clinicians to develop dosing p

292 eas HNF4alpha transcriptionally up-regulates CYP2C9 via proximal sites.

293 We examined whether CYP2C9/VKORC1 genotypes provide information about warfar

294 The P450 enzyme CYP2C9 was attached to each of these nanopillars, and co

295 n of flurbiprofen and naproxen metabolism by CYP2C9 were also observed.

296 Molecular dynamics (MD) simulations of CYP2C9 were performed to study the range of energeticall

297 R of CYP2C9 and the endogenous expression of CYP2C9 were suppressed by transfection of hsa-miR-128-3p

298 tial inhibitory activities against DprE1 and CYP2C9, which provides insights for development of a cli

299 This report examines the regulation of CYP2C9 with respect to two specific receptors thought to

300 110L and F114L mutants on the interaction of CYP2C9 with several of its substrates as well as the pot