ライフサイエンスコーパス: CYP3A4

1 ered pharmaceuticals that are metabolized by CYP3A4.

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

3 isible spectra of N-methylritonavir bound to CYP3A4.

4 key human P450 involved in drug metabolism: CYP3A4.

5 s of ritonavir bound per mole of inactivated CYP3A4.

6 llent selectivities over CYP11B1, CYP19, and CYP3A4.

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

8 tor roscovitine stimulated the expression of CYP3A4.

9 ntrations of statins that are metabolized by CYP3A4.

10 direct transcriptional regulator of hepatic CYP3A4.

11 ndent inhibition only occurred in CYP2C8 and CYP3A4.

12 iver transplantation; both are substrates of CYP3A4.

13 s were present in incubations with CYP1A2 or CYP3A4.

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

15 ferentially and regioselectively oxidized by CYP3A4.

16 clobetasol to the heme in CYP3A5 but not in CYP3A4.

17 he drug-metabolizing cytochrome P450 enzyme, CYP3A4.

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

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

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

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

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

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

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

25 CYP3A4, a cytochrome P450 enzyme regulated by the nuclea

26 development of an isoform-specific probe for CYP3A4, a key cytochrome P450 isoform responsible for th

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

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

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

30 None of these compounds altered CYP3A4 activity.

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

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

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

34 We also have investigated the mechanisms of CYP3A4 allostery using biophysical and advanced spectros

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

36 tion of several genes and inhibition of both CYP3A4 and CYP1A2, matching effects observed with whole

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

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

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

40 Preliminary evaluation of the CYP3A4 and CYP2D6 inhibitory activity in optimized ligan

41 of the effect in representative cytochromes (CYP3A4 and CYP2D6) demonstrated insignificant inhibitory

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

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

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

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

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

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

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

49 The human cytochrome P450 (CYP) enzymes CYP3A4 and CYP3A5 metabolize most drugs and have high si

50 indicated differences in plasticity between CYP3A4 and CYP3A5 that favor alternative ritonavir confo

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

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

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

54 much larger active site than substrate-free CYP3A4 and displays an open substrate access channel.

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

56 er trajectory of the helix F-F' connector in CYP3A4 and more extensive pai-CH interactions between ph

57 ressed rifampicin-induced gene expression of CYP3A4 and multidrug resistance protein 1, as well as th

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

59 Studying the regulation/induction of CYP3A4 and PXR is critical in toxicology and drug-drug i

60 inhibitor, significantly increases the basal CYP3A4 and PXR levels in 24 hours.

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

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

63 Finally, the acyclic amines inactivated CYP3A4 and this liability was addressed by modifications

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

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

66 for metabolism by human cytochrome P450 3A4 (CYP3A4) and human aldehyde oxidase (hAOX) for more in-de

67 2E1) or this region and alpha2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for b5 M

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

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

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

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

72 17beta-HSD2, 17beta-HSD7, 17beta-HSD12, and CYP3A4, and did not stimulate the proliferation of estro

73 transcription factor function in regulating CYP3A4, and it appears to be acting at least in part in

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

104 an be used for drug induction studies, where CYP3A4, CYP1A2, CYP2C9, and CYP2C19 inductions were achi

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

106 ty, and Caco-2 penetration and did not block CYP3A4, CYP2D6 isoenzymes, or P-glycoprotein.

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

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

109 otility factor receptor) as a relevant E3 in CYP3A4, CYP3A23, and CYP2E1 UPD.

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

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

112 3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, and CYP3A7 was decreased.

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

114 most important CYP subfamily in humans, and CYP3A4/CYP3A5 genetic variants contribute to inter-indiv

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

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

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

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

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

120 found to modulate RTV hepatotoxicity through CYP3A4-dependent pathways involved in RTV bioactivation,

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

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

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

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

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

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

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

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

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

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

131 n comparison to Caco-2, it displays improved CYP3A4 expression and induction capability.

132 rforin is one constituent of SJW that alters CYP3A4 expression by activation of the nuclear receptor

133 ts demonstrate a role for unliganded ESR1 in CYP3A4 expression consistent with unliganded ESR1 signal

134 ropose a hierarchical regulatory network for CYP3A4 expression directed by ESR1 through self-regulati

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

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

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

138 role of transcription factors in regulating CYP3A4 expression, and used molecular genetics methods (

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

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

141 PXR in confluent cells resulted in decreased CYP3A4 expression.

142 pairs, triplets, and quadruplets involved in CYP3A4 expression.

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

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

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

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

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

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

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

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

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

152 2, and aryl hydrocarbon receptor, but not of CYP3A4, hepatocyte nuclear factor-4alpha, or pregnane X

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

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

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

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

157 The extensive role of CYP3A4 in drug metabolism reflects in part the plasticit

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

159 sfully applied to the real-time detection of CYP3A4 in living cells and zebrafish.

160 strated the essential roles of human PXR and CYP3A4 in RTV hepatotoxicity, which can be applied to gu

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

162 role of CYP1A2, CYP2A6, CYP2B6, CYP2E1, and CYP3A4 in the metabolism of chiral PCBs.

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

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

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

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

167 ctivity-relationships (SARs) of the unwanted CYP3A4 induction and the desired HBV capsid inhibition t

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

169 Effect on CYP3A4 induction was observed.

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

171 Tangeretin was the only compound causing CYP3A4 induction while CYP3A4 inhibition was most likely

172 capsid inhibitor with significantly reduced CYP3A4 induction, excellent anti-HBV activity, favorable

173 scribed herein is a new approach to mitigate CYP3A4 induction.

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

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

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

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

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

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

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

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

182 only compound causing CYP3A4 induction while CYP3A4 inhibition was most likely the result of additive

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

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

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

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

187 ssessing low microsomal stability and potent CYP3A4 inhibition.

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

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

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

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

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

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

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

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

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

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

198 CYP3A4 is an abundant and catalytically dominant human l

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

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

201 Whereas CYP3A4 is predominantly expressed in the liver, CYP3A5 i

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

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

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

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

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

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

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

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

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

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

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

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

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

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

216 pands metabolic capabilities and can augment CYP3A4-mediated drug metabolism, thereby reducing drug e

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

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

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

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

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

222 action potential when enhanced expression of CYP3A4 modifies clearance of concomitantly applied subst

223 /3A7 mouse model showed in vivo induction of CYP3A4 mRNA and protein by [4-chloro-6-(2,3-xylidino)-2-

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

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

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

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

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

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

230 omes (rat and human), and 32 did not inhibit CYP3A4 nor CYP2C9.

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

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

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

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

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

236 ough glucuronidation in addition to that via CYP3A4 oxidation.

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

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

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

240 of estrone 3-sulfate and for their impact on CYP3A4 promoter transactivation.

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

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

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

244 Alterations of CYP3A4 protein turnover can influence clinically relevan

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

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

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

248 mplex differs substantially from that of the CYP3A4-ritonavir complex.

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

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

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

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

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

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

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

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

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

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

263 Moreover, ESR1 and known CYP3A4 TFs mutually regulate each other.

264 In addition to known CYP3A4 TFs, estrogen receptor alpha (ESR1) emerges as ke

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

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

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

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

269 cription factors and regulatory networks for CYP3A4, the main drug metabolizing enzymes in liver.

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

271 heme-clobetasol complex in CYP3A5 but not in CYP3A4, thus explaining the CYP3A5 selectivity of clobet

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

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

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

278 in the PXR protein significantly induced the CYP3A4 transcription.

279 Cytochrome P450 3A4 isoform (CYP3A4) transcription is controlled by hepatic transcrip

280 This CYP3A4 turnover involves endoplasmic reticulum-associate

281 icantly induces the expression of CYP2B6 and CYP3A4, two shared target genes of hCAR and human PXR (h

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

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

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

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

286 al two-photon fluorescent substrate (NN) for CYP3A4 was effectively selected using ensemble-based vir

287 AR-KO HepaRG cells, PB-induced expression of CYP3A4 was markedly repressed by genetic knockdown or ph

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

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

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

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

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

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

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

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

300 ssion and also analyzed for cytochrome P450 (CYP3A4) zonation and glycogen accumulation through PAS s