ライフサイエンスコーパス: P450 3A4

1 t potency for inhibition of human cytochrome P450 (3A4).

2 n drug molecules to metabolism by cytochrome P450 3A4.

3 erivative everolimus (SDZ-RAD) by cytochrome P450 3A4.

4 line engineered to express human cytochrome P450 3A4.

5 nhibitor, was investigated using recombinant P450 3A4.

6 t the entire molecule (M(r) 521) fits within P450 3A4.

7 able of conferring the P450 3A5 phenotype on P450 3A4.

8 substrate recognition site model of Gotoh to P450 3A4.

9 terpreted using a three-dimensional model of P450 3A4.

10 of several drugs that are largely cleared by P450 3A4.

11 activity of a key enzyme of drug metabolism, P450 3A4.

12 ocriptine (one bromine atom) with cytochrome P450 3A4.

13 sA, NC1153 was not metabolized by cytochrome P450 3A4.

14 syltransferase (UGT) isoforms and cytochrome P450 3A4.

15 None of the P450 enzymes examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be i

16 Cytochromes P450 3A4, 2D6, and 2C9 metabolize a large fraction of dr

17 the functional activity of human cytochrome P450s 3A4, 2E1, 2B6, 2C9, 2C19, and 2D6 was also examine

18 P450 3A4 and not the 6alpha, indicating that P450 3A4 abstracts hydrogen and rebounds oxygen only at

19 inactivated P450 3A4 pertain to two distinct P450 3A4 active site domains.

20 Limited successes in P450 3A4 active-site structure studies have been achieve

21 less, and can be used to confirm and measure P450 3A4 activity and can also be used as a guide for de

22 Cytochrome P450 3A4 activity was estimated using the carbon-14 [14C

23 ted with a significant decline in cytochrome P450 3A4 activity, which is predictive of clinically imp

24 atic microsomal metabolism of 1- and 4-NP to P450 3A4, although a minor role for P450 1A2 cannot be r

25 major drug-metabolizing enzymes (cytochrome P450 3A4 and 2D6 [CYP3A4 and CYP2D6]) were also measured

26 ceprevir is a strong inhibitor of cytochrome P450 3A4 and 3A5 (CYP3A4/5).

27 Cytochromes P450 3A4 and 3A5, the dominant drug-metabolizing enzymes

28 by incubation with cholesterol; the level of P450 3A4 and cell viability were not altered under the c

29 baculovirus and bacterial membranes in which P450 3A4 and NADPH-P450 reductase were coexpressed; the

30 Only the 6beta-hydrogen was removed by P450 3A4 and not the 6alpha, indicating that P450 3A4 ab

31 ions and the presence of combined cytochrome P450 3A4 and P-glycoprotein inhibitors in the Rivaroxaba

32 those treated with >/= 1 combined cytochrome P450 3A4 and P-glycoprotein inhibitors.

33 i) values for blocking the binding to ferric P450 3A4 and the oxidation of several substrates may be

34 tes was catalyzed by P450 3A4 (for 5-MeC) or P450s 3A4 and 1A2 (for 6-MeC).

35 nderstand the structural differences between P450s 3A4 and 3A5, the structure of 3A5 complexed with r

36 )-position is selectively catalyzed by human P450s 3A4 and 3A5, with the latter being more efficient,

37 9-hydroxylation reactions were attributed to P450 3A4, and 18- and 19-hydroxydihydrotestosterone were

38 erol is both a substrate and an inhibitor of P450 3A4, and a model is presented to explain the kineti

39 s an effective photoaffinity ligand of human P450 3A4, and mass spectrometry data demonstrating the e

40 P450 3A4 apparently prefers AFB1 3alpha-hydroxylation, w

41 d, 14C-heme labeled, recombinant human liver P450 3A4 as the target of CuOOH-mediated inactivation, a

42 norbuprenorphine formation was detected for P450s 3A4, as previously described, but also for 3A5, 3A

43 ), rat liver (RLM) and bicistronic human-cyt P450 3A4 (bicis.-3A4) microsomes as enzyme sources.

44 The P450 3A4 binding process is more complex than a two-stat

45 YPFP-NH(2) was not oxidized by P450 3A4 but blocked binding of the substrates testoster

46 of a saturated 8,9-bond, was not oxidized by P450 3A4 but could inhibit AFB1 oxidation.

47 Mechanism-based inactivation of human liver P450 3A4 by L-754,394, a Merck compound synthesized as a

48 In contrast, alpha-naphthoflavone stimulated P450 3A4 by selectively binding and activating an otherw

49 ors, inhibitors, or substrates of cytochrome P450 3A4 can be expected.

50 homotropic and heterotropic cooperativity in P450 3A4-catalyzed oxidations is not well understood, an

51 Cholesterol inhibited the P450 3A4-catalyzed oxidations of nifedipine and quinidin

52 imethyl-2-aminofluorene N-oxygenation, human P450 3A4-catalyzed quinidine N-oxygenation, rat P450 2B1

53 P450 3A4 catalyzes the metabolic clearance of a large nu

54 d activates gene transcription of cytochrome p450-3A4, causing significant botanical-drug interaction

55 ctra indicated a K(d) value of 8 muM for the P450 3A4-cholesterol complex.

56 Cytochrome P450 3A4 (CYP3A4) activity and docetaxel pharmacokinetic

57 and topiramate, enhances hepatic cytochrome P450 3A4 (CYP3A4) activity, and can decrease serum conce

58 onally homogeneous 1:1 complex of cytochrome P450 3A4 (CYP3A4) and cytochrome P450 reductase solubili

59 cells and increased expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance 1 (MDR1).

60 conformational landscape of human cytochrome P450 3A4 (CYP3A4) by electron paramagnetic resonance and

61 as a mechanism-based inhibitor of cytochrome P450 3A4 (CYP3A4) by forming adducts with the apoprotein

62 This study employed a cytochrome P450 3A4 (CYP3A4) crystal structure (Protein Data Bank e

63 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics

64 e hepatocyte-like cells exhibited cytochrome P450 3A4 (CYP3A4) enzyme activity, secreted urea, uptake

65 cancer drug, in interaction with cytochrome P450 3A4 (CYP3A4) enzyme and multiwalled carbon nanotube

66 N can significantly down-regulate cytochrome P450 3A4 (CYP3A4) expression in human primary hepatocyte

67 Allosteric mechanisms in human cytochrome P450 3A4 (CYP3A4) in oligomers in solution or monomeric

68 tituent alleviated time-dependent cytochrome P450 3A4 (CYP3A4) inhibition.

69 Utilization of the cytochrome P450 3A4 (CYP3A4) inhibitor ritonavir as a pharmacoenhan

70 Cytochrome P450 3A4 (CYP3A4) inhibitors ritonavir and cobicistat, c

71 Human cytochrome P450 3A4 (CYP3A4) is a key xenobiotic-metabolizing enzym

72 The membrane-bound protein cytochrome P450 3A4 (CYP3A4) is a major drug-metabolizing enzyme.

73 Cytochrome P450 3A4 (CYP3A4) is a major enzymatic determinant of dr

74 Human cytochrome P450 3A4 (CYP3A4) is a major hepatic and intestinal enzy

75 Cytochrome P450 3A4 (CYP3A4) is the dominant P450 enzyme involved i

76 Cytochrome P450 3A4 (CYP3A4) is the dominant xenobiotic metabolizin

77 Cytochrome P450 3A4 (CYP3A4) is the most abundant membrane-associat

78 The drug metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is thought to be involved in the metab

79 Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than a

80 Cytochrome P450 3A4 (CYP3A4) metabolizes more than 50% of prescribe

81 Cytochrome P450 3A4 (CYP3A4) plays a critical role in the metabolis

82 Statins primarily metabolized by cytochrome P450 3A4 (CYP3A4) reportedly reduce clopidogrel's metabo

83 homotropic cooperativity in human cytochrome P450 3A4 (CYP3A4) we studied the interactions of the enz

84 or human drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) were explored with fluorescence resona

85 One of such enzymes, cytochrome P450 3A4 (CYP3A4), plays critical roles in drug metaboli

86 t conformational heterogeneity of cytochrome P450 3A4 (CYP3A4), the kinetics of dithionite-dependent

87 to determine hepatic activity of cytochrome P450 3A4 (CYP3A4), the main docetaxel-metabolizing enzym

88 Inhibition of cytochrome P450 3A4 (CYP3A4), the major drug metabolizing enzyme, b

89 Monomeric cytochrome P450 3A4 (CYP3A4), the most prevalent cytochrome P450 in

90 ory region of the PXR target gene cytochrome P450 3A4 (CYP3A4), with a concomitant methylation of arg

91 g binding to human membrane-bound cytochrome P450 3A4 (CYP3A4).

92 olchicine and known inhibitors of cytochrome P450 3A4 (CYP3A4)/P-glycoprotein (cyclosporine, ketocona

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

94 ents having a variant genotype of cytochrome P450 3A4 displayed higher blood concentrations of parent

95 s showed that ritonavir inhibited cytochrome P450 3A4 enzyme (CYP3A4) in liver microsomes.

96 osterone and demonstrates the sensitivity of P450 3A4, even with its large active site, to small chan

97 P450 3A4 exhibits a relatively large substrate-binding c

98 inhibitors and substrates of the cytochrome P450 3A4 family.

99 e hydroxymethyl metabolites was catalyzed by P450 3A4 (for 5-MeC) or P450s 3A4 and 1A2 (for 6-MeC).

100 Of several human P450s examined, only P450 3A4 formed this product.

101 Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylat

102 PXR activates cytochrome P450 3A4 gene expression upon binding to rifampicin (Rif

103 being only a minor reaction, indicating that P450 3A4 has considerable control over the course of ste

104 and used to probe the catalytic mechanism of P450 3A4: (i) 2,2,4,6,6-(2)H(5); (ii) 6,6-(2)H(2); (iii)

105 sting of their potential to label cytochrome P450 3A4 in a light-dependent fashion.

106 residues at positions 364-377 of cytochrome P450 3A4 in determining steroid hydroxylation or stimula

107 c efficiencies were similar for P450 2D6 and P450 3A4 in the presence of cytochrome b(5) with (R)-ret

108 Midazolam appears to be able to bind to P450 3A4 in two modes, one corresponding to the testoste

109 g, HIC) but showed time-dependent cytochrome P450 3A4 inhibition, possibly related to morpholine ring

110 lavone allowed analysis of an initial ligand-P450 3A4 interaction that does not cause a perturbation

111 Cytochrome P450 3A4 is a drug-metabolizing enzyme of extraordinaril

112 Thus P450 3A4 is an enzyme with regioselective flexibility bu

113 Cytochrome P450 3A4 is an important mediator of drug catabolism tha

114 Cytochrome P450 3A4 is generally considered to be the most importan

115 nding of interaction of drug inhibitors with P450 3A4 is important in predicting clinical drug-drug i

116 Cytochrome P450 (P450) 3A4 is an extensively studied human enzyme involve

117 Cytochrome P450 (P450) 3A4 is the most abundant human P450 and oxidizes a

118 Cytochrome P450 (P450) 3A4 is the most abundant human P450 enzyme and has

119 on by phenytoin and rifampicin of cytochrome P450 3A4 isoform that converts monocrotaline to toxic in

120 human liver microsomes, did not inhibit the P450 3A4 isozyme, and had low protein binding (18.22% fo

121 on drugs that are susceptible to cytochrome P450 3A4-mediated hydrogen radical abstraction followed

122 molecule's ability to competitively inhibit P450 3A4-mediated oxidative metabolism of midazolam with

123 Cytochrome P450 3A4 metabolizes terfenadine, astemizole, carbamazep

124 A P450 3A4 model based on these peptide studies contains a

125 e-depleted C98S/C239S/C377S/C468A cytochrome P450 3A4 mutant designated CYP3A4(C58,C64) allowed site-

126 Moreover, the P450 3A4 mutant N206S most closely mimicked P450 3A5, no

127 Of the P450 3A4 mutants examined, P107S, F108L, N206S, L210F, V

128 In addition, some of these P450 3A4 mutations that affected AFB1 regioselectivity h

129 same patterns were seen with AFB1 in a fused P450 3A4-NADPH-P450 reductase protein.

130 roughput assay for measuring the activity of P450 3A4, one of the key enzymes involved in drug metabo

131 ptidase-C digestion of the CuOOH-inactivated P450 3A4 pertain to two distinct P450 3A4 active site do

132 ms containing purified recombinant bacterial P450 3A4, positive cooperativity was seen in oxidations

133 etric binding of the inactivating species to P450 3A4 precluded the direct identification of a covale

134 drug-drug interactions due to its cytochrome P450 3A4 profile.

135 high (D)k value was also seen with a slower P450 3A4 reaction, the O-dealkylation of 7-benzyloxyquin

136 P450 3A4 reduction was examined in liver microsomes, a r

137 utations resulted in a significant switch of P450 3A4 regioselectivity toward that of P450 3A5.

138 The structure of P450 3A4 should facilitate a better understanding of the

139 Only P450 3A4 showed substantial catalytic activity for methy

140 d to weaker binding of YPFP-NH(2) to ferrous P450 3A4 than to the ferric form.

141 on amino acid residues 210-216 of cytochrome P450 3A4, the major drug-metabolizing enzyme of human li

142 ly regulates the transcription of cytochrome P450 3A4, the major human drug-metabolizing enzyme.

143 ase inhibitor and an inhibitor of cytochrome P450 3A4, the major human hepatic drug-metabolizing enzy

144 irected mutagenesis and computer modeling of P450 3A4, the most likely location of effector binding i

145 Cytochrome P450 (P450) 3A4, the major catalyst involved in human drug oxi

146 is a prototypic reaction of cytochrome P450 (P450) 3A4, the major human P450.

147 If cholesterol is a substrate of P450 3A4, then it follows that it should also be an inhi

148 ) also argues that room should be present in P450 3A4 to bind more than one smaller ligand in the "te

149 The structure of P450 3A4 was determined by x-ray crystallography to 2.05

150 L-754,394 that had been adducted to P450 3A4 was hydrolyzed under the conditions used for SD

151 Specifically, P450 3A4 was responsible for the formation of 3-hydroxy-

152 r products formed during the inactivation of P450 3A4 were the monohydroxylated and the dihydrodiol m

153 d U-46619, induced spectral changes in human P450 3A4 with K(s) values of 240 +/- 20 and 130 +/- 10 m

154 The finding that P450 3A4 with one altered residue, Leu210 --> Ala, can h

155 The interactions of P450 3A4 with several structurally diverse inhibitors we

156 tative substrate recognition sites (SRSs) of P450 3A4 with the corresponding amino acid of P450 3A5.