ライフサイエンスコーパス: CYP3A4

1 key human P450 involved in drug metabolism: CYP3A4.

2 ferentially and regioselectively oxidized by CYP3A4.

3 s of ritonavir bound per mole of inactivated CYP3A4.

4 llent selectivities over CYP11B1, CYP19, and CYP3A4.

5 metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4.

6 tor roscovitine stimulated the expression of CYP3A4.

7 ntrations of statins that are metabolized by CYP3A4.

8 direct transcriptional regulator of hepatic CYP3A4.

9 ndent inhibition only occurred in CYP2C8 and CYP3A4.

10 iver transplantation; both are substrates of CYP3A4.

11 as been linked to the potent inactivation of CYP3A4.

12 that in corresponding cells expressing only CYP3A4.

13 s the most likely intermediate to inactivate CYP3A4.

14 he drug-metabolizing cytochrome P450 enzyme, CYP3A4.

15 ered pharmaceuticals that are metabolized by CYP3A4.

16 sions of CAR and its target genes CYP2B6 and CYP3A4.

17 isible spectra of N-methylritonavir bound to CYP3A4.

18 ween miR-122 and the 3'UTR of the CYP1A2 and CYP3A4.

19 The specific case of [CYP3A4.17-click] highlights the risk of interpreting CYP

20 This study investigated the influence of the CYP3A4*22, CYP3A5*3, and ABCB1 exons 12, 21, and 26 poly

21 Tryptic digestion of the CYP3A4-[(3)H]ritonavir incubations exhibited an adducted

22 for ABCB1 1236C>T, 2677 G>T/A, and 3435C>T; CYP3A4 -392A>G; CYP3A5 6986A>G and 14690G>A; IL-10 -1082

23 P450, family 3, subfamily A, polypeptide 4 (CYP3A4) -392A>G, cytochrome P450, family 3, subfamily A,

24 Furthermore, a humanized CYP3A4/3A7 mouse model showed in vivo induction of CYP3A

25 levated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased.

26 CYP3A4/5 protein content was unchanged (57 +/- 13% vs. 5

27 (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent

28 ng inhibitor of cytochrome P450 3A4 and 3A5 (CYP3A4/5).

29 Cytochrome P4503A4 (CYP3A4), a major human drug-metabolizing enzyme, is resp

30 P3A4 with close contacts to the B-B' loop of CYP3A4, a substrate recognition site.

31 type II ligand that perfectly fits into the CYP3A4 active site cavity and irreversibly binds to the

32 ain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respec

33 these drugs may rise to harmful levels when CYP3A4 activity is inhibited.

34 in human hepatocyte-like C3A cells (enhanced CYP3A4 activity/albumin synthesis) when in co-culture wi

35 amate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum concentrations

36 Knowledge of how CYP3A4 adjusts and reshapes the active site to regiosele

37 Clarithromycin is an inhibitor of CYP3A4 and azithromycin is not, which makes comparisons

38 ate pregnane X receptor (PXR) and subsequent CYP3A4 and CYP2C9 expression in hPSC-derived and isolate

39 rate that Cyb5 can be a major determinant of CYP3A4 and CYP2D6 activity in vivo, with a potential imp

40 e predicted to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively.

41 CYP1A2, CYP3A4 and CYP2E1 mRNA levels were decreased, while miRN

42 sent a regulatory response to modify CYP1A2, CYP3A4 and CYP2E1 translation due to cellular stress and

43 lls suppressed protein expression of CYP1A2, CYP3A4 and CYP2E1.

44 The partition ratios for the inactivation of CYP3A4 and CYP3A5 by dronedarone are 51.1 and 32.2, and

45 the partition ratios for the inactivation of CYP3A4 and CYP3A5 by NDBD are 35.3 and 36.6.

46 Testosterone protected both CYP3A4 and CYP3A5 from inactivation by dronedarone and N

47 ite N-desbutyl dronedarone (NDBD) inactivate CYP3A4 and CYP3A5 in a time-, concentration-, and NADPH-

48 conclusion, dronedarone and NDBD inactivate CYP3A4 and CYP3A5 via unique dual mechanisms of MBI and

49 MBI of CYP3A4 and CYP3A5 was further supported by the discovery

50 of CsA, AM1, AM9, and AM1c with recombinant CYP3A4 and CYP3A5 were performed to evaluate the formati

51 hermore, coexpression in HepG2 cells of both CYP3A4 and gp78, but not its functionally inactive RING-

52 ations of [(3)H]ritonavir with reconstituted CYP3A4 and human liver microsomes resulted in a covalent

53 CYP3A4 and its mammalian liver CYP3A orthologs are endop

54 them subconfluent resulted in a decrease in CYP3A4 and PXR expression back to levels observed in sub

55 in proliferating control cells increased the CYP3A4 and PXR protein levels.

56 cluding CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial steroidogenic enzymes, CYP17 and

57 This effect was independent of CYP3A4 and was negated by cotreatment with the drug effl

58 cromolar affinity and inhibitory potency for CYP3A4 and, thus, could serve as templates for synthesis

59 2E1) or this region and alpha2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for b5 M

60 (CYP2R1, CYP27B1) and inactivation (CYP24A1, CYP3A4) and the newest physiological roles of vitamin D.

61 ycin, inhibit cytochrome P450 isoenzyme 3A4 (CYP3A4), and inhibition increases blood concentrations o

62 found to form covalent adducts with CYP2E1, CYP3A4, and CYP2C9.

63 ARalpha-mediated induction of CYP1A, CYP2C8, CYP3A4, and CYP4A11 genes, suggesting a dominant-negativ

64 17beta-HSD2, 17beta-HSD7, 17beta-HSD12, and CYP3A4, and did not stimulate the proliferation of estro

65 fampicin further increased the expression of CYP3A4, and siRNA-mediated knock-down of PXR in confluen

66 ither cords of hepatocytes (express albumin, CYP3A4, and transferrin), branching ducts of cholangiocy

67 against CYP2E1 modified by INH, 14 had anti-CYP3A4 antibodies, and 10 had anti-CYP2C9 Abs.

68 ring though a covalent bond to Lys257 of the CYP3A4 apoprotein.

69 ater from the sixth axial ligand position of CYP3A4 as expected for a type II ligand.

70 We identified CYP3A4 as the major enzyme involved in the metabolism of

71 Our findings reveal that such CYP3A4 Asp/Glu/Ser(P)/Thr(P) surface clusters are indeed

72 To assess reversible CYP3A4 autoinduction, the expanded part of the study tes

73 we present a 2.15 A crystal structure of the CYP3A4-BEC complex in which the drug, a type I heme liga

74 , linear dichroism measurements performed on CYP3A4 bound to Nanodisc membranes were used to characte

75 The X-ray structures of CYP3A4 bound to the rationally designed inhibitors provi

76 y lowers affinity and inhibitory potency for CYP3A4 but also leads to multiple binding modes.

77 ibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive inhibitor of CYP1A2,

78 it a clinically significant interaction with CYP3A4, but that modulation of bioavailability through P

79 inhibition of cytochrome P450 (CYP) 2C19 and CYP3A4 by meropenem, suggesting that during meropenem tr

80 resented here demonstrate that inhibition of CYP3A4 by ritonavir occurs by CYP3A4-mediated activation

81 However, the mechanism of inhibition of CYP3A4 by ritonavir remains unclear.

82 Given the potent inhibition of CYP3A4 by ritonavir, subtherapeutic doses of ritonavir a

83 ygen species did not prevent inactivation of CYP3A4 by ritonavir.

84 onal landscape of human cytochrome P450 3A4 (CYP3A4) by electron paramagnetic resonance and fluoresce

85 nism-based inhibitor of cytochrome P450 3A4 (CYP3A4) by forming adducts with the apoprotein.

86 t in CYP enzymology, two in vitro aspects of CYP3A4 catalysis are still not well understood, namely,

87 The expression of CYP3A4 changes during liver development and may be affec

88 nts demonstrated an inhibition effect on the CYP3A4, clearly observed as a diminished electrocatalyti

89 A biologically realistic model of CYP3A4, complete with its transmembrane helix and a memb

90 ed related results, it is suggested that for CYP3A4, computing tools may allow rapid identification o

91 rmation of a covalent adduct specifically to CYP3A4, confirmed by radiometric liquid chromatography-t

92 iver microsomes was strongly correlated with CYP3A4 content and midazolam hydroxylation activity.

93 We conclude that the 3'-end processing of CYP3A4 contributes to the quantitative regulation of CYP

94 ings strongly suggest that the mechanisms of CYP3A4 cooperativity involve a conformational transition

95 losomes further demonstrated that CYP2D6 and CYP3A4 could transform tyrosol into hydroxytyrosol.

96 cture/activity relationships rather than the CYP3A4 crystal structure.

97 This study employed a cytochrome P450 3A4 (CYP3A4) crystal structure (Protein Data Bank entry 1W0E)

98 ed potassium channel protein inhibition, and CYP3A4 (CYP = cytochrome P450) inhibition are influenced

99 Apo-b(5) enhances the activities of CYP3A4, CYP2A6, CYP2C19, and CYP17A1 but not that of CYP

100 ple human metabolizing-enzyme genes (such as CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2E1 and UGT1A4) in TH

101 rmation of mixed oligomers in CYP3A4/CYP3A5, CYP3A4/CYP2E1, and CYP3A5/CYP2E1 pairs and demonstrated

102 tide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), N

103 Here we probe oligomerization of human CYP3A4, CYP3A5, and CYP2E1 in microsomal membranes.

104 3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased.

105 Midazolam is primarily metabolized by the CYP3A4/CYP3A5 enzymes.

106 observed the formation of mixed oligomers in CYP3A4/CYP3A5, CYP3A4/CYP2E1, and CYP3A5/CYP2E1 pairs an

107 mediate complex between dronedarone/NDBD and CYP3A4/CYP3A5, partial recovery of enzyme activity by po

108 Our results suggest that CYP3A4-dependent 25OHD(3) metabolism may play an importa

109 rs (n = 6) with rifampin selectively induced CYP3A4-dependent 4beta,25(OH)(2)D(3), but not CYP24A1-de

110 evealed that MCF7 cells synthesize EETs in a CYP3A4-dependent manner.

111 We now report a novel CYP3A4-dependent pathway, the 4-hydroxylation of 25-hydr

112 ent prodrug metabolism which was found to be CYP3A4-dependent.

113 However, mice expressing human CYP3A4 did not process vemurafenib to a greater extent t

114 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many

115 is primarily caused by CYP1A2-, CYP2E1-, and CYP3A4-driven conversion of APAP into hepatotoxic metabo

116 are metabolized by the cytochrome P450 3A4 (CYP3A4; EC 1.14.13.97) enzyme.

117 col (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity.

118 lucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic sta

119 te-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake of low-de

120 ug, in interaction with cytochrome P450 3A4 (CYP3A4) enzyme and multiwalled carbon nanotubes (MWCNTs)

121 y for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confi

122 a regulatory mechanism explaining changes of CYP3A4 expression and activity during hepatocyte differe

123 CYP3A4 expression in breast cancer correlates with decre

124 the data strongly suggest that the increased CYP3A4 expression in confluent Huh7 cells is caused by t

125 o CYP3A drug-metabolism activity and hepatic CYP3A4 expression in humans as well as mouse and human h

126 FGF21) in the molecular mechanism regulating CYP3A4 expression in NAFLD.

127 , mouse and cellular NAFLD models with lower CYP3A4 expression, circulating FGF21, or hepatic FGF21 m

128 ression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their potential to

129 PXR in confluent cells resulted in decreased CYP3A4 expression.

130 ional Ser/Thr protein phosphorylation primes CYP3A4 for ubiquitination.

131 PXR-mediated induction of CYP1A, CYP2B6 and CYP3A4 (for CAR and PXR), and CYP2C8 (for PXR) gene expr

132 In contrast to CYP26A1, CYP3A4 formed the 4-OH-RA enantiomers in a 1:1 ratio and

133 or (PXR), a key transcriptional regulator of CYP3A4 Furthermore, decreased nuclear PXR was observed i

134 ontributes to the quantitative regulation of CYP3A4 gene expression through alternative polyadenylati

135 Reporter analysis revealed that the CYP3A4 gene was transcriptionally activated during confl

136 in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition.

137 s reduced by >50% in hepatic microsomes from CYP3A4-HBN mice compared with controls.

138 increased 4- and 5.7-fold, respectively, in CYP3A4-HBN mice.

139 2, and aryl hydrocarbon receptor, but not of CYP3A4, hepatocyte nuclear factor-4alpha, or pregnane X

140 detoxifying enzymes including GSTA2, GSTP1, CYP3A4, HO-1, MRP1, and MRP5.

141 results indicate that apo b(5) can dock with CYP3A4 in a manner analogous to that of holo b(5), so el

142 molecule bound at the distal surface of the CYP3A4 in a prior x-ray crystal structure.

143 The critical role of Arg446 on CYP3A4 in binding to cyt b(5) and/or cytochrome P450 red

144 tially induces the expression of CYP2B6 over CYP3A4 in HPHs, although endogenous expression of these

145 chromes in the brain and work in tandem with CYP3A4 in the liver.

146 , which requires a full understanding of the CYP3A4 inactivation mechanisms and the unraveling of pos

147 stigations of analogs of ritonavir, a potent CYP3A4 inactivator and pharmacoenhancer, we have built a

148 petitive or mixed competitive-noncompetitive CYP3A4 inactivator.

149 romycin with a statin that is metabolized by CYP3A4 increases the risk for statin toxicity.

150 ng bioactivation, PXR activation, as well as CYP3A4 induction and inhibition led to the identificatio

151 In conclusion, tumor CYP3A4 induction by sorafenib is a novel mechanism to ac

152 Effect on CYP3A4 induction was observed.

153 ), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed.

154 f miR-18a-5p, and this preceded the onset of CYP3A4 induction.

155 reduction in the extent of hPXR target gene (CYP3A4) induction by rifampin and rilpivirine.

156 g duration of action and improved profile of CYP3A4 inhibition and induction compared to aprepitant.

157 o better understand the structural basis for CYP3A4 inhibition and the ligand binding process, we inv

158 g interaction is the suspected cause whereby CYP3A4 inhibition by boceprevir led to increased exposur

159 drug-interactions (DDI), as 2 is a victim of CYP3A4 inhibition caused by its exclusive clearance path

160 CYP3A4 inhibition may lead to drug-drug interactions, to

161 '' pocket of BACE1 remediated time-dependent CYP3A4 inhibition of earlier analogues in this series an

162 n anti-HIV therapy, the precise mechanism of CYP3A4 inhibition remains unclear.

163 In this chemical series, absence of CYP3A4 inhibition was obtained at the expense of satisfa

164 patinib exposure, including the food effect, CYP3A4 inhibition, and dose fractionation.

165 nalysis included Caco-2 permeability/efflux, CYP3A4 inhibition, hERG inhibition, and rat microsomal e

166 We found that CYP3A4 inhibition, hERG inhibition, Caco-2 permeability,

167 nd structural insights into the mechanism of CYP3A4 inhibition, we investigated the ritonavir binding

168 ssessing low microsomal stability and potent CYP3A4 inhibition.

169 leviated time-dependent cytochrome P450 3A4 (CYP3A4) inhibition.

170 gravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC),

171 gravir (EVG) has been co-formulated with the CYP3A4 inhibitor cobicistat (COBI), emtricitabine (FTC),

172 and such conversion was attenuated by potent CYP3A4 inhibitor ketoconazole.

173 Utilization of the cytochrome P450 3A4 (CYP3A4) inhibitor ritonavir as a pharmacoenhancer for an

174 safety warnings regarding concurrent use of CYP3A4 inhibitors and calcium-channel blockers.

175 and for demonstrating the potential of known CYP3A4 inhibitors to prevent metabolism of methadone.

176 ions, there is a need for development of new CYP3A4 inhibitors with improved pharmacochemical propert

177 Cytochrome P450 3A4 (CYP3A4) inhibitors ritonavir and cobicistat, currently a

178 We investigated the mechanism of CYP3A4 interaction with three desoxyritonavir analogues,

179 lencing, providing a potential mechanism for CYP3A4 involvement in breast cancer cell growth.

180 These studies indicate that CYP3A4 is a highly active AA epoxygenase that promotes S

181 CYP3A4 is an abundant and catalytically dominant human l

182 that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for

183 he binding affinity of N-methylritonavir for CYP3A4 is pH-dependent.

184 Human cytochrome P450 3A4 (CYP3A4) is a key xenobiotic-metabolizing enzyme that oxi

185 Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzyme that ox

186 Cytochrome P450 3A4 (CYP3A4) is the dominant P450 enzyme involved in human dr

187 Cytochrome P450 3A4 (CYP3A4) is the dominant xenobiotic metabolizing CYP.

188 Cytochrome P450 3A4 (CYP3A4) is the most abundant membrane-associated isoform

189 d to be a typical O(2)-derived metabolite of CYP3A4, is in fact produced by a highly unusual hydrolys

190 The metabolism of [(3)H]ritonavir by CYP3A4 leads to the formation of a covalent adduct speci

191 WT1 gene expression also correlates with CYP3A4 levels and is associated with poorer response to

192 the importance of polar interactions in the CYP3A4-ligand association.

193 de deeper insights into the mechanism of the CYP3A4-ligand interaction.

194 ive RING-finger mutant, resulted in enhanced CYP3A4 loss greater than that in corresponding cells exp

195 ither of the E3s, coupled with the increased CYP3A4 loss on gp78 or CHIP coexpression, suggests that

196 xpression of FGF21 resulted in reduced liver CYP3A4 luciferase reporter activity in mice and decrease

197 ther confirmed that the interacting sites on CYP3A4 (Lys96, Lys127, and Lys421) are functionally impo

198 downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC.

199 We solved the 2.7 A crystal structure of the CYP3A4-MDZ complex, where the drug is well defined and o

200 inhibition of CYP3A4 by ritonavir occurs by CYP3A4-mediated activation and subsequent formation of a

201 Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testos

202 ide convincing evidence for the mechanism of CYP3A4-mediated dehydrogenation of raloxifene to a react

203 Furthermore, the rate of CYP3A4-mediated metabolism of 17-click was comparable to

204 ydroxyraloxifene is produced exclusively via CYP3A4-mediated oxygenation and provide convincing evide

205 studies were utilized to carefully elucidate CYP3A4-mediated oxygenation versus dehydrogenation of ra

206 y the concentration-dependent restoration of CYP3A4-mediated triazolam turnover and CYP2D6-mediated b

207 pathway may be involved in decreased hepatic CYP3A4 metabolic activity in NAFLD.

208 mor dependent involving induction of tumoral CYP3A4 metabolism, with host pretreatment alone unable t

209 Cytochrome P450 3A4 (CYP3A4) metabolizes more than 50% of prescribed drugs.

210 (total turnover of approximately 2 pmol/pmol CYP3A4/min) but not hydroxylase products (+/-)-15-, (+/-

211 ty to investigate the effect of the modified CYP3A4 model on metabolite prediction with the ligand do

212 /3A7 mouse model showed in vivo induction of CYP3A4 mRNA and protein by [4-chloro-6-(2,3-xylidino)-2-

213 rase reporter activity in mice and decreased CYP3A4 mRNA expression and activity in cultured Huh7 hep

214 kinase in Huh7 cells caused de-repression of CYP3A4 mRNA expression with FGF21 treatment.

215 udy was to examine expression of alternative CYP3A4 mRNA transcripts in hepatocytes in response to de

216 A sequencing (RNA-Seq) were used to identify CYP3A4 mRNA transcripts.

217 oma cell line Huh7 substantially induces the CYP3A4 mRNA, protein, and activity levels.

218 of crystallographic structures available for CYP3A4, no structural information for its membrane-bound

219 process vemurafenib to a greater extent than CYP3A4-null animals, suggesting that other pregnane X re

220 othesized that the intersubunit interface in CYP3A4 oligomers is similar to that observed in the crys

221 e results of intermolecular cross-linking of CYP3A4 oligomers with thiol-reactive bifunctional reagen

222 demonstrated that the association of either CYP3A4 or CYP3A5 with CYP2E1 causes activation of the la

223 one methide with a carboxylic acid moiety of CYP3A4, or other proteins in the reconstituted system.

224 aused by its exclusive clearance pathway via CYP3A4 oxidation in humans.

225 ough glucuronidation in addition to that via CYP3A4 oxidation.

226 and known inhibitors of cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (cyclosporine, ketoconazole, rito

227 from time 0 to infinity for colchicine plus CYP3A4/P-glycoprotein inhibitors versus colchicine alone

228 rations of colchicine, but not the reference CYP3A4/P-glycoprotein inhibitors, were determined, and t

229 on of the approved on-label regimen of known CYP3A4/P-glycoprotein inhibitors.

230 nt is continued during therapy with multiple CYP3A4/P-glycoprotein inhibitors.

231 ere coadministered with most of the selected CYP3A4/P-glycoprotein inhibitors.

232 tive metabolite through the cytochrome P450 (CYP3A4) pathway, which also metabolizes calcium channel

233 ntified, which revealed that only CYP2C8 and CYP3A4 possess accessible cysteine residues near the act

234 , non-ligand-dependent regulation of PXR and CYP3A4, possibly of physiologic and pharmacological sign

235 that p53 inhibits the binding of PXR to the CYP3A4 promoter.

236 -substrate recruitment, an important step in CYP3A4 proteasomal degradation.

237 enzymatic biosensors have been obtained with CYP3A4 protein immobilized on MWCNTs as recognition biom

238 Alterations of CYP3A4 protein turnover can influence clinically relevan

239 Decreased PXR binding to the CYP3A4 proximal promoter was found in FGF21-treated Huh7

240 Although silencing of CYP3A4 reduces nuclear Tyr(P)-705-Stat3, (+/-)-14,15-EET

241 adducts to Cys225 and Cys239 for CYP2C8 and CYP3A4, respectively.

242 and 0.81 muM and 0.20 min(-1) for CYP2C8 and CYP3A4, respectively.

243 By inhibiting CYP3A4, ritonavir increases plasma concentrations of oth

244 determined the 2.0 A X-ray structure of the CYP3A4-ritonavir complex.

245 Intriguingly, CYP3A4 Ser(P)/Thr(P) and ubiquitinated Lys residues resi

246 We have documented that CYP3A4 Ser/Thr phosphorylation (Ser(P)/Thr(P)) by PKA an

247 oxicity and inhibition of hepatic CYP2A6 and CYP3A4 showed that 44 fulfills first safety criteria and

248 CYP3A4 silencing blocks the cell cycle at the G(2)/M che

249 selectively rescues breast cancer cells from CYP3A4 silencing in a concentration-dependent fashion an

250 3 (Tyr-705) phosphorylation was inhibited by CYP3A4 silencing, providing a potential mechanism for CY

251 rprobe distances in the oligomers of labeled CYP3A4 single-cysteine mutants.

252 In this work, monomeric CYP3A4 solubilized in Nanodiscs has been studied for its

253 r, we have built a pharmacophore model for a CYP3A4-specific inhibitor.

254 tes was induced by rifampin and inhibited by CYP3A4-specific inhibitors.

255 eral ligand-binding site observed in certain CYP3A4 structures.

256 ent was incorporated into a well-established CYP3A4 substrate and mechanism-based inactivator, 17-alp

257 predict the sites of metabolism of the known CYP3A4 substrate raloxifene.

258 re is very limited structural information on CYP3A4-substrate interactions available to date.

259 One of the CYP3A4 substrates is bromoergocryptine (BEC), a dopamine

260 Proteolytic digests of CYP2C8 and CYP3A4 Supersomes revealed adducts to Cys225 and Cys239

261 lls, it induces the expression of CYP2B6 and CYP3A4, targets of hCAR and the pregnane X receptor (PXR

262 uding PXR activation, CYP2C9 inhibition, and CYP3A4 TDI, several compounds were advanced into in vivo

263 esire to reduce time-dependent inhibition of CYP3A4 (TDI) by members of this structural class.

264 ed nitrostilbene to be a weaker inhibitor of CYP3A4 than resveratrol, and stronger than dimethoxy-nit

265 quilibrium between open and closed states of CYP3A4 that involves a pronounced change at the interfac

266 ine hepatic activity of cytochrome P450 3A4 (CYP3A4), the main docetaxel-metabolizing enzyme.

267 Inhibition of cytochrome P450 3A4 (CYP3A4), the major drug metabolizing enzyme, by dietary

268 lso potently inactivates cytochrome P4503A4 (CYP3A4), the major human drug-metabolizing enzyme.

269 For the inactivation of CYP3A4, the inactivator concentration at the half-maximu

270 trations of other anti-HIV drugs oxidized by CYP3A4 thereby improving clinical efficacy.

271 oncentrations of other HIV drugs oxidized by CYP3A4, thereby extending their clinical efficacy.

272 orm selectivity was strongly associated with CYP3A4 time-dependent inhibition (TDI).

273 all molecule inhibitors that could attenuate CYP3A4 time-dependent inhibition commonly observed with

274 ound 1, to attenuate hERG inhibition, remove CYP3A4 time-dependent inhibition, and improve pharmacoki

275 Etoposide is metabolized by CYP3A4 to etoposide catechol, which can be further oxidi

276 and produced more protein compared with the CYP3A4 transcript with canonical 3'-UTR.

277 The CYP3A4 transcript with shorter 3'-UTR was more stable an

278 real time quantitative PCR revealed that the CYP3A4 transcript with shorter 3'-UTR was preferentially

279 in the PXR protein significantly induced the CYP3A4 transcription.

280 This CYP3A4 turnover involves endoplasmic reticulum-associate

281 complexes, thereby controlling the timing of CYP3A4 ubiquitination and endoplasmic reticulum-associat

282 ific endogenous ligand of PPARalpha, induced CYP3A4 (up to 4-fold) and other biotransformation genes

283 and -III) within approximately 12 kb of the CYP3A4 upstream sequence.

284 A CYP3A4 variant is associated with a lower risk of etopos

285 for a direct interaction between SWCNTs and CYP3A4 was also provided.

286 CYP3A4 was profiled for NADPH-dependent arachidonic acid

287 CYP3A4 was the predominant source of 25OHD(3) hydroxylat

288 ve (P = .0001), although hepatic activity of CYP3A4 was unchanged (P = .26).

289 riazolam 4-hydroxylation (probe reaction for CYP3A4) was reduced by >50% in hepatic microsomes from C

290 brane orientation, and lipid interactions of CYP3A4, we have employed a combined experimental and sim

291 models of interaction of holo/apo b(5) with CYP3A4 were built using the identified interacting sites

292 interactions of both holo and apo b(5) with CYP3A4 were investigated and compared for the first time

293 enzymatic activities of CYP2C2, CYP2C8, and CYP3A4 were slightly higher in PGRMC1-deficient cells.

294 rug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) were explored with fluorescence resonance energy

295 Membrane binding of the globular domain in CYP3A4, which appears to be independent of the presence

296 As verapamil is a substrate for CYP3A4, which is induced by rifampin, we evaluated the p

297 The extracts also inhibited the activity of CYP3A4, whose expression was induced by 1,25-dihydroxyvi

298 were predicted to bind to the same groove on CYP3A4 with close contacts to the B-B' loop of CYP3A4, a

299 his, we crossed mice humanized for CYP2D6 or CYP3A4 with mice carrying a hepatic Cyb5 deletion.

300 roscopic investigation of the interaction of CYP3A4 with N-methylritonavir, an analog of ritonavir, w