ライフサイエンスコーパス: CYP3A

1 CYP3A activation of MMDX abolished the parent drug's res

2 CYP3A activity is the sum activity of the family of CYP3

3 CYP3A enzymes are extremely versatile and are inducible

4 CYP3A enzymes metabolize endogenous hormones and chemoth

5 CYP3A inhibition was determined from the impairment of n

6 CYP3A metabolic activity was significantly induced by Mi

7 CYP3A metabolism generates epipodophyllotoxin catechol a

8 CYP3A substrates inhibited the protein aggregation and s

9 CYP3A, the most important family of drug-metabolizing en

10 CYP3A-activated MMDX displayed a comparatively high intr

11 CYP3A-dependent oxidative metabolism of testosterone (TS

12 CYP3A-mediated ipso-addition is also implicated in the r

13 cipitation analyses revealed a basal 52% 35S-CYP3A loss over 6 h, which was stabilized by both protea

14 s dexamethasone [strong cytochrome P-450 3A (CYP3A) inducer] or triamcinolone acetonide (weak CYP3A i

15 ensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit

16 es and/or inhibitors of cytochrome P-450 3A (CYP3A).

17 n intestinal and hepatic cytochrome P450 3A (CYP3A) activity.

18 e-treated rats will form cytochrome P450 3A (CYP3A) aggregates when incubated at 37 degrees C.

19 rile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chem

20 Cytochrome P450 3A (CYP3A) is an enzyme of paramount importance to drug meta

21 Cytochrome P450 3A (CYP3A) is the most abundant CYP450 enzyme in the liver a

22 Human cytochrome P450 3A (CYP3A) members are major drug-metabolizing enzymes in th

23 Many genes of the cytochrome P450 3A (CYP3A) subfamily, including several human and rat isofor

24 rease in the activity of cytochrome P450 3A (CYP3A), which catalyzes side-chain hydroxylations of bil

25 lyzed by enzymes such as cytochrome P450 3A (CYP3A).

26 The human liver cytochromes P450 3A (CYP3As), orthologous to the rat glucocorticoid inducible

27 rea under the time-concentration curve for a CYP3A substrate.

28 T>C (P<0.05) and 4beta-hydroxycholesterol, a CYP3A activity marker (adjusted R(2)=0.47).

29 of patients with a cytotoxic agent that is a CYP3A substrate, and clinical outcome (Pinteraction = 0.

30 basis underlying the functional effects of a CYP3A haplotype on urinary estrone glucuronide (E1G) lev

31 ic p97 knockdown almost completely abrogated CYP3A extraction into the cytosol, resulting in a signif

32 se of P-gp inhibitors with minimal or absent CYP3A inhibitory effects should decrease the impact of d

33 th biochemically and genetically to activate CYP3A genes, while similar studies have established cons

34 phan receptor CAR was also found to activate CYP3A through previously defined SXR/PXR response elemen

35 Stabilization of a functionally active CYP3A after RNAi knockdown of either of the E3s, coupled

36 d in increased levels of functionally active CYP3A, thereby challenging the previous notion that E3 r

37 ohn's wort (SJW) has been reported to affect CYP3A expression and activity in rats.

38 97 interactions were greatly magnified after CYP3A suicidal inactivation (which accelerates UPD), and

39 those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the stu

40 meat are substrates for inducible CYP1A and CYP3A enzymes and for P-glycoprotein.

41 display an increased expression of CYP2B and CYP3A proteins.

42 They were reduced by inhibition of CYP2D and CYP3A enzymes.

43 chrome P450 enzymes of subfamilies CYP2D and CYP3A were inhibited before intravenous injection of [(1

44 the relationship between hepatic CYP2E1 and CYP3A activities and their messenger RNA (mRNA) expressi

45 conducted a study to compare the CYP2E1 and CYP3A activities in 20 individuals with moderate alcohol

46 RNA levels did not correlate with CYP2E1 and CYP3A activities.

47 quivalent levels of immunoreactive CYP3A and CYP3A activity as measured by erythromycin N-demethylase

48 CYP3A inhibition and the IC50s for P-gp and CYP3A inhibition allowed comparison of the relative inhi

49 mine whether the ability to inhibit P-gp and CYP3A is, in fact, linked and whether specific P-gp inhi

50 nd between the extent of P-gp inhibition and CYP3A inhibition, and the ratio of the IC50 for CYP3A in

51 tion, as well as of CYP3A protein levels and CYP3A-dependent testosterone 6beta-hydroxylation.

52 Microsomal CYP2E1, CYP2C-like, and CYP3A-like protein levels were also decreased in both st

53 bundant P-450 enzyme in the human liver, and CYP3A enzymes metabolize more than 50% of prescription d

54 or inducers of CYP2B (PB; phenobarbital) and CYP3A enzymes (DX; dexamethasone), isoforms induced by c

55 ted by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influ

56 1, but other P450 enzymes such as CYP2C8 and CYP3As also contribute to atRA 4-hydroxylation.

57 Triacetyloleandomycin and anti-CYP3A antibody inhibited midazolam hydroxylation by 53%

58 cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of ster

59 We used midazolam and fexofenadine to assess CYP3A (intestinal and hepatic) and drug transport, respe

60 levels and tested for an association between CYP3A genotype and outcome in patients with chronic lymp

61 rsible and reversible interactions with both CYP3A isoforms and further unraveled the molecular deter

62 ever, no information is available for bovine CYP3A (bCYP3A).

63 MMDX was rapidly activated by CYP3A at low ( approximately 1-5 nM) prodrug concentrati

64 gs demonstrate that MMDX can be activated by CYP3A metabolism to a potent, long-lived, and cell-perme

65 (a reaction characteristically catalyzed by CYP3A enzymes) was estimated to be somewhat lower than t

66 of C-C bond cleavage: one bond is cleaved by CYP3A-mediated ipso-addition of oxygen to a C(sp(2)) sit

67 aluation of MBI-associated hepatotoxicity by CYP3A.

68 ion of cortisol to 6 beta-hydroxycortisol by CYP3A may mediate increased tubular reabsorption of sodi

69 2C19, respectively, with some involvement by CYP3A.

70 oxides, which are efficiently metabolized by CYP3A.

71 one or more anticancer drugs metabolized by CYP3A.

72 mice, and showed that DDC is metabolized by CYP3A.

73 to the expected and previously characterized CYP3A pathway; rather, it is associated with a robust in

74 Therefore, we characterized CYP3A activity in a bank of microsomes from human kidney

75 We compared CYP3A metabolism of erythromycin (a Pgp substrate) using

76 By contrast, no corresponding CYP3A stabilization was detected with either ALD inhibit

77 strate specificities of PXR and its critical CYP3A target gene.

78 on days 1, 5, and 12 and analyzed for CYP1A, CYP3A, and P-glycoprotein messenger RNA (mRNA) and prote

79 and immunoreactive protein but not of CYP1A, CYP3A, or CYP4A.

80 r bilirubin metabolism and excretion (CYP2B, CYP3A, MRP2, MRP3, UGT1A, and glutathione S-transferase

81 cess was specific for P-450s CYP1A2, CYP2E1, CYP3A, and CYP4A and was not demonstrated to be involved

82 evels several female-predominant liver CYPs (CYP3A, CYP2B, and testosterone 6beta-hydroxylase).

83 The cytochrome CYP3A gene products, expressed in mammalian liver, are e

84 12alpha-triol (triol), a cholesterol-derived CYP3A substrate, is a potent PXR agonist that effectivel

85 Little detectable CYP3A accumulated in the cytosol, even after concomitant

86 of the major drug-metabolizing P450s, i.e., CYP3A, CYP2C, and CYP2D.

87 gest that after extended periods of elevated CYP3A expression, microsomal factors are induced that ca

88 titative detection and imaging of endogenous CYP3A activity in various living systems, thereby provid

89 This prompted us to ask whether endogenous CYP3A substrates also serve as PXR ligands.

90 of the hydroxylating cytochrome P450 enzyme CYP3A and promoting detoxification.

91 Analysis of individual cDNA-expressed CYP3A enzymes revealed that rat CYP3A1 and human CYP3A4

92 with a corresponding approximately 2.5-fold CYP3A stabilization.

93 3A inhibition, and the ratio of the IC50 for CYP3A inhibition to the IC50 for P-gp inhibition varied

94 o develop a two-photon fluorescent probe for CYP3A that is involved in the metabolism of more than ha

95 es was 10-fold higher than that required for CYP3A stabilization, we examined the effect of MG132 (0-

96 or, lithocholic acid is also a substrate for CYP3A enzymes.

97 , as we show here, a metabolic substrate for CYP3A hydroxylation.

98 thromycin, a widely used model substrate for CYP3A.

99 numerous medications that are substrates for CYP3A and Pgp.

100 Determination of the apparent Ki values for CYP3A inhibition and the IC50s for P-gp and CYP3A inhibi

101 The rat, mouse, and hamster CYP3A genes are mixed among several rodent CYP3A subclad

102 onazole, potent inhibitor of gut and hepatic CYP3A, has been shown to increase tacrolimus bioavailabi

103 Because hepatic CYP3A activity also seems to be induced during human pre

104 As expected, hepatic CYP3A activity was reduced in cirrhosis.

105 )CO(2) in the breath as a measure of hepatic CYP3A activity.

106 tion, there was no alteration in the hepatic CYP3A activity, but the reduced midazolam oral bioavaila

107 represents at least 50% of the total hepatic CYP3A content in people polymorphically expressing CYP3A

108 e induced that catalyze the formation of HMM CYP3A conjugates that contain ubiquitin.

109 and the cytosol-dependent degradation of HMM CYP3A.

110 ubstrates inhibited the formation of the HMM CYP3A and the cytosol-dependent degradation of HMM CYP3A

111 sol did result in the degradation of the HMM CYP3A bands in a process that was not blocked by proteas

112 in, suggesting that the formation of the HMM CYP3A may have resulted from conjugation to itself or a

113 s of tryptic peptides indicated that the HMM CYP3A was in molar excess to ubiquitin, suggesting that

114 system that forms high-molecular-mass (HMM) CYP3A, CYP2E1, and ubiquitin conjugates, but does not al

115 /polymerase chain reaction analysis of human CYP3A gene expression.

116 dy to demonstrate that a member of the human CYP3A gene family contains an enhancer that binds the GC

117 Immunoprecipitated CYP3A contained HMM ubiquitin.

118 mals had equivalent levels of immunoreactive CYP3A and CYP3A activity as measured by erythromycin N-d

119 Importantly, CYP3A induction mimics findings in humans, but our resul

120 Five variants showed differences in CYP3A catalytic activity: three CYP3A28 SNVs reduced TST

121 terindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many

122 1 do not display a corresponding increase in CYP3A activity and are stricken with the disease cerebro

123 h E3s are indeed physiologically involved in CYP3A ERAD/UPD in cultured rat hepatocytes.

124 , thereby documenting a major role of p97 in CYP3A extraction and delivery to the 26 S proteasome dur

125 standard chemotherapy regimens that include CYP3A substrates may not be optimal for the approximatel

126 Cytochrome P450 (CYP) enzymes, including CYP3A, and multiple intestinal and hepatic drug transpor

127 tery of PXR target genes in liver, including CYP3A, Oatp2, and UGT1A1.

128 ohexy lamine (BIBX 79) selectively increased CYP3A mRNA and immunoreactive protein contents, with max

129 R is necessary and sufficient to both induce CYP3A enzymes and confer resistance to toxicity by LCA,

130 ally diverse collection of drugs that induce CYP3A.

131 Furthermore, MG-262-induced CYP3A stabilization was associated with its polyubiquity

132 Ro 48-8071-inducible CYP3A mRNA expression was restored when pravastatin-trea

133 t cyclase inhibitors are capable of inducing CYP3A expression in primary cultured rat and mouse hepat

134 ward these nuclear receptors could influence CYP3A gene expression.

135 p inhibitors with limited ability to inhibit CYP3A can be identified.

136 All compounds inhibited CYP3A with apparent Ki values of between 0.3 and 76 micr

137 at prodrug cleavage proceeded via an initial CYP3A-catalyzed oxidation to an intermediate ring-opened

138 ty, but its effect on hepatic and intestinal CYP3A in humans is not known.

139 ate alcohol consumption may cause intestinal CYP3A induction.

140 dazolam as a result of diminished intestinal CYP3A activity.

141 5-D3 and VDR induce expression of intestinal CYP3A by binding of the activated VDR-RXR heterodimer to

142 New animal models are needed to investigate CYP3A functions, especially for drug metabolism.

143 an inactivator of cytochrome P450 isoenzyme CYP3A without anti-HIV activity) and a new integrase inh

144 glucocorticoid and can be inhibited by known CYP3A inhibitors.

145 rate that the down-regulation of CYP2C-like, CYP3A-like and CYP2E1 proteins and mRNAs, in the endotox

146 CYP3A4 and its mammalian liver CYP3A orthologs are endoplasmic reticulum (ER)-anchored

147 ndicate that teleost, diapsid, and mammalian CYP3A genes have undergone independent diversification a

148 ients are lacking, whereas clearance of many CYP3A drug substrates may be decreased, potentially lead

149 centration-dependence of Ro 48-8071-mediated CYP3A mRNA induction corresponded to the cellular conten

150 Cyclase inhibitor-mediated CYP3A mRNA induction was eliminated when primary culture

151 ceptor PXR and demonstrated that it mediates CYP3A induction.

152 microsomes were measured by LC-MS/MS methods.CYP3A activity in hepatic microsomes exhibited a signifi

153 here is a significant increase in microsomal CYP3A dependent steroid 6 beta-hydroxylase activity but

154 o be a regioselective inhibitor of midazolam CYP3A metabolism.

155 Glucocorticoids modulate CYP3A and P-glycoprotein in preclinical models, but thei

156 Moreover, CYP3A plays an important role in chemical metabolism, to

157 Most CYP3A diversity is the product of recent gene duplicatio

158 wed by significant increases in CYP3A1 mRNA, CYP3A-immunoreactive microsomal protein and total micros

159 t-5-en-17-one.HCl (U18666A) to induce murine CYP3A were abolished in hepatocyte cultures prepared fro

160 Such native CYP3A-p97 interactions were greatly magnified after CYP3

161 cin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medicat

162 with which other steroidal and nonsteroidal CYP3A inducers have been shown to compete, indicates tha

163 this study demonstrate that there is a novel CYP3A member expressed in human tissues, although its re

164 amplification technology was used on a novel CYP3A-like exon 1 sequence detected during the reverse t

165 The activity of CYP3A was measured in hepatic and intestinal microsomes,

166 The expression and activity of CYP3A, an enzyme responsible for active androgen clearan

167 Addition of CYP3A substrates inhibited the formation of the HMM CYP3

168 The amount of CYP3A protein in liver was inversely related to the gene

169 Immunoblotting analyses of CYP3A immunoprecipitates after PFA-cross-linking reveale

170 Analysis of CYP3A expression and activity was performed on lacrimal

171 lophosphamide 4-hydroxylation, as well as of CYP3A protein levels and CYP3A-dependent testosterone 6b

172 Our characterization of CYP3A degradation has indicated that CYPs 3A incur ubiqu

173 efficient discovery and characterization of CYP3A-induced MBI in natural systems.

174 th the number of days of coadministration of CYP3A inhibitors (r=0.30; p=0.006).

175 ilability can be an important determinant of CYP3A metabolism of numerous medications that are substr

176 used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, t

177 n that E3 recognition and subsequent ERAD of CYP3A proteins required ab initio their structural and/o

178 MDR1, might influence hepatic expression of CYP3A or other cytochromes P-450 (P-450s) because Pgp ca

179 ad reduced basal and inducible expression of CYP3A.

180 nf4alpha had reduced or absent expression of CYP3A.

181 determinant of drug-inducible expression of CYP3A.

182 oprotein (Pgp) could influence the extent of CYP3A-mediated metabolism of erythromycin, a widely used

183 ctivity is the sum activity of the family of CYP3A genes, including CYP3A5, which is polymorphically

184 e stress is a key factor in the formation of CYP3A aggregates in incubated microsomes and in a recons

185 es in liver expression of different forms of CYP3A.

186 turnover and time-dependent inactivation of CYP3A isoforms in the liver without compromising the pot

187 ibited potent time-dependent inactivation of CYP3A, with the mechanism of inactivation occurring thou

188 nd Cmin by 46%, consistent with induction of CYP3A by efavirenz.

189 of the mouse PXR gene abolishes induction of CYP3A by prototypic inducers such as dexamethasone or pr

190 The induction of CYP3A enzymes is species-specific, and we have postulate

191 erexpressing clones, rifampicin induction of CYP3A mRNA and protein was decreased and required greate

192 of rifampicin were required for induction of CYP3A proteins, and the magnitude of CYP3A induction was

193 use of erythromycin and strong inhibitors of CYP3A should be avoided.

194 any P-gp inhibitors are potent inhibitors of CYP3A, a varying degree of selectivity is present.

195 h the concurrent use of strong inhibitors of CYP3A.

196 sterdam had dramatically increased levels of CYP3A protein as well as other P-450s examined and of th

197 The magnitude of CYP3A induction by rifampicin was compared in the human

198 tion of CYP3A proteins, and the magnitude of CYP3A induction was greater at all doses of rifampicin i

199 e midazolam clearance, a surrogate marker of CYP3A-mediated drug metabolism, in critically ill childr

200 d no relationship with these measurements of CYP3A, but changed proportionally to expression of mdr1.

201 was measured by monitoring the metabolism of CYP3A probe substrates-namely, 7-benzyloxyquinoline (BQ)

202 es, dictates the species-specific pattern of CYP3A inducibility.

203 tructure of the gene dictates the pattern of CYP3A inducibility.

204 The regiospecificity of CYP3A-catalyzed oxygen ipso-addition under environmental

205 The role of Pgp in regulation of CYP3A expression in vivo was analyzed in mice carrying a

206 ights into the transcriptional regulation of CYP3A in the liver.

207 e but apparent compensatory up-regulation of CYP3A, CYP2B, and some ABC transporters that is consiste

208 aling pathways involved in the regulation of CYP3A, CYP2C, and CYP2D, which are critical enzymes in d

209 This is the first report of CYP3A-mediated C-C bond cleavage in drug metabolism via

210 ctivity while having greatly reduced risk of CYP3A induction in humans.

211 e physiological and pharmacological roles of CYP3A, especially in drug and chemical metabolism in viv

212 We analyzed the 5'-flanking sequences of CYP3A genes from the rat (CYP3A23, CYP3A2), rabbit (CYP3

213 to the substrate-dependent stabilization of CYP3A observed in vivo.

214 rtant in substrate-mediated stabilization of CYP3A.

215 eptor, rather than the promoter structure of CYP3A genes, dictates the species-specific pattern of CY

216 Tacrolimus, a substrate of CYP3A, has low and variable bioavailability similar to c

217 NA was increased by insulin, whereas that of CYP3A was unaffected.

218 tudy helps provide a better understanding of CYP3A regulation and offers novel clues for the role of

219 m of SXR causes constitutive upregulation of CYP3A gene expression and enhanced protection against to

220 A or vitamin D induced expression in vivo of CYP3A, a cytochrome P450 enzyme that detoxifies LCA in t

221 the species-specific effects of compounds on CYP3A gene expression.

222 und a biphasic MG132 concentration effect on CYP3A turnover: Stabilization at 5 to 10 muM with marked

223 her than deconvoluting the effect of P-gp on CYP3A-mediated metabolism.

224 ntration-dependent proteasomal inhibition on CYP3A turnover in cultured primary rat hepatocytes.

225 Mallotus furetianus ethanol extract (MFE) on CYP3A activity in rats.

226 We evaluated the effect of uremia on CYP3A and transporter expression in vitro by incubating

227 gene encoding cytochrome P450 3A oxygenase (CYP3A) causes a prominent class of dangerous drug-drug i

228 Metabolism by cytochrome P4503A (CYP3A) and P-glycoprotein (P-gp)-mediated efflux are two

229 ulators and substrates of cytochrome P4503A (CYP3A).

230 To assess the in vivo relevance of this p97-CYP3A association, we used lentiviral shRNAs to silence

231 efficacy of drugs metabolized by CYP3A4, pan-CYP3A inhibitors such as ritonavir are often co-administ

232 Intriguingly, the accumulated parent CYP3A was functionally active, indicating that p97 can r

233 s potency, hERG inhibition, CNS penetration, CYP3A time-dependent inhibition, and kinase selectivity

234 dicating that p97 can regulate physiological CYP3A content and thus influence its clinically relevant

235 by effectively regulating the physiological CYP3A content and consequently its function.

236 rong support for placement of the guinea pig CYP3A genes within the rodent CYP3A diversification.

237 mpound was unexpectedly found to be a potent CYP3A inducer in human hepatocytes, and thus further che

238 CYP3A5 is the primary CYP3A subfamily enzyme expressed in the human kidney and

239 -hydroxymidazolam (1'-OHM) as a prototypical CYP3A-catalyzed reaction.

240 Luciferase induction by the prototypical CYP3A inducer pregnenolone 16alpha-carbonitrile was rest

241 zed purified rat CYP2E1 but not purified rat CYP3A were detected by enzyme-linked immunosorbent assay

242 Hence, critically ill patients receiving CYP3A substrate drugs may be at risk of increased drug l

243 r-kappaB activation and consequently reduced CYP3A protein stability.

244 cid levels in the intestine by up-regulating CYP3A enzymes with 1,25(OH)2 D3 analogs may have therape

245 Consistent with the protein results, CYP3A catalytic activity measured as midazolam 1'- and 4

246 r CYP3A genes are mixed among several rodent CYP3A subclades, indicative of a complex history involvi

247 the guinea pig CYP3A genes within the rodent CYP3A diversification.

248 een WT and LCN mice in small intestinal (SI) CYP3A levels at 6 hours after the treatment.

249 cestral vertebrate genome contained a single CYP3A gene.

250 tor of CYP2C9) or troleandomycin (a specific CYP3A inhibitor) did not increase inhibition beyond that

251 bonyl-Leu-Leu-Leu-B(OH)(2) (MG262) stabilize CYP3A proteins.

252 short half-life and how substrates stabilize CYP3A.

253 At these high MG132 concentrations, such CYP3A suppression could be due to ER stress induction, s

254 , MG132 is indeed cytotoxic and can suppress CYP3A synthesis, a result confirmed by confocal immunofl

255 binding to cytochrome P450 isoenzyme system CYP3A induced extreme prolongation of tacrolimus metabol

256 rofiling by RNAi silencing demonstrates that CYP3A or 2C8 gene expression is specifically required fo

257 e after oral administration, suggesting that CYP3A function is not changed by ESRD.

258 The CYP3A enzymes metabolize a wide variety of chemically di

259 The CYP3A genes reside on chromosome 7q21 in a multigene clu

260 The CYP3A inhibitors used in the study were nitroimidazole a

261 The CYP3A subfamily of hepatic cytochromes P450, being engag

262 why MDZ is predominantly metabolized by the CYP3A enzyme subfamily.

263 more, heteroactivation was suppressed by the CYP3A inhibitor ketoconazole in a concentration-dependen

264 Of the cytochrome P450 enzymes, the CYP3A subfamily is the most abundant in liver and intest

265 indings revealed the molecular basis for the CYP3A induction class of drug-drug interactions and prov

266 Variation in the CYP3A enzymes, which act in drug metabolism, influences

267 hrough a DNA response element located in the CYP3A promoter, and is activated by a structurally diver

268 The CYP3 gene family includes the CYP3A and CYP3B subfamilies.

269 ol fails to activate human PXR or induce the CYP3A-salvage pathway.

270 nsport is a critical element influencing the CYP3A inductive response.

271 id-or rifampicin-inducible expression of the CYP3A cytochromes P450, the dominant froms of this super

272 erindividual variability and ontogeny of the CYP3A enzymes, the most abundant phase I drug-metabolizi

273 is the ubiquitously expressed member of the CYP3A family in renal tissue.

274 ntagonist that induces the expression of the CYP3A family of steroid hydroxylases and modulates stero

275 expression of the xenobiotic enzymes of the CYP3A family.

276 The apparent coordinated coexpression of the CYP3A gene family and P-glycoprotein in the LS180 cells

277 major glucocorticoid-inducible member of the CYP3A gene family, have been identified.

278 plete coding sequence of a new member of the CYP3A gene subfamily, CYP3A43.

279 Members of the CYP3A subfamily represent the dominant CYP forms express

280 Two vital enzymes of the CYP3A subfamily, CYP3A4 and CYP3A5, are differentially e

281 In the presence of substrate, the CYP3A-mediated lipid hydroperoxide metabolism is inhibit

282 of the activated VDR-RXR heterodimer to the CYP3A PXR response element and promoting gene transcript

283 egulate the mRNA of enzymes belonging to the CYP3A subfamily, increasing the metabolism of a variety

284 tentiation ratios directly correlated to the CYP3A-dependent testosterone 6beta-hydroxylase activity

285 Hyperiplant and Rebalance transactivated the CYP3A reporter 3.8-fold and 2.8-fold, respectively, and

286 ling showed that most of SNVs were distal to CYP3A active site, suggesting indirect effects on the ca

287 epatic protein, including but not limited to CYP3A and tryptophan 2,3-dioxygenase protein syntheses.

288 CYP3A5 represented greater than 50% of total CYP3A content in nearly all of the livers and jejuna tha

289 ant accumulation of parent and ubiquitinated CYP3A species that were firmly ER-tethered.

290 Raloxifene, a drug known to undergo CYP3A-mediated reactive metabolite formation and time-de

291 ; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those wh

292 antibiotic medications who had formerly used CYP3A inhibitors.

293 of metabolite profiles and experiments using CYP3A-specific inhibitors indicated that CYP3A4 was the

294 with medications that are metabolized using CYP3A and causes reversible declines in estimated glomer

295 clearances were used to measure the in vivo CYP3A activity, and chlorzoxazone (CHZ) oral clearance w

296 hat NAFLD is associated with reduced in vivo CYP3A drug-metabolism activity and hepatic CYP3A4 expres

297 A) inducer] or triamcinolone acetonide (weak CYP3A inducer) produced dose-dependent increases in luci

298 Such overlap raises the question of whether CYP3A inhibition is an intrinsic characteristic of P-gp

299 e studies provide a mechanistic model of why CYP3A has a relatively short half-life and how substrate

300 Animals treated with CYP3A inducers or inhibitor showed accelerated or dimini