ライフサイエンスコーパス: CYP17

1 chrome P450 17alpha-hydroxylase-17,20-lyase (CYP17).

2 e to androstenedione compared with wild-type CYP17.

3 understanding of the reactions catalysed by CYP17.

4 specific cofactor requirements than Xenopus CYP17.

5 interactions of redox partner proteins with CYP17.

6 on CYP11B1 (steroid-11beta-hydroxylase) and CYP17 (17alpha-hydroxy/17,20-lyase), compound 22 was fou

7 In the past year abiraterone acetate, a CYP17 (17alpha-hydroxylase/17, 20 lyase) inhibitor, rece

8 o of the bands were immunoreactive with anti-CYP17 (54 kDa) or anti-CYP21 (52 kDa) antibody.

9 utility of inhibiting cytochrome P450 17A1 (CYP17), a cytochrome p450 enzyme that is required for th

10 Here, we examined the role of CYP17, a key enzyme mediating sex steroid synthesis, in

11 entiated overexpressing steroidogenic enzyme CYP17, a theca cell-specific marker.

12 The CYP17 A2 allele and the HSD17B1 A allele were considered

13 , among women hetero- and homozygous for the CYP17 A2 allele compared to A1/A1 women.

14 he with breast cancer may be modified by the CYP17 A2 allele.

15 Women who carry the CYP17 A2/A2 genotype were about half as likely as women

16 d the natural substrate pregnenolone, in the CYP17 active site together with molecular dynamics simul

17 Additionally, ovarian CYP17 activity was present exclusively in oocytes, altho

18 ding the first 28 amino acid residues with a CYP17 amino-terminal sequence and by adding a polyhistid

19 more effective antiandrogens, inhibitors of CYP17, an enzyme required for androgen synthesis, inhibi

20 sed the association between the A2 allele of CYP17 and breast cancer risk in a case-control study nes

21 variants of the estrogen-metabolizing genes CYP17 and catechol O-methyl transferase (COMT) with risk

22 1A.V2 also reduced androgen biosynthesis and CYP17 and CYP11A1 mRNA when added to the medium of cultu

23 expression of the fetal Leydig cell markers Cyp17 and Cyp11a1 was reduced in heterozygous Sf1-defici

24 respectively, and a high selectivity toward CYP17 and CYP11B1.

25 It showed no inhibition of CYP17 and CYP19 and no mutagenic effects.

26 he genes encoding two steroidogenic enzymes, CYP17 and CYP19, and examining their expression patterns

27 rat CYP11B1 and good selectivity over human CYP17 and CYP19, it is a promising candidate for further

28 YP3A4 and the crucial steroidogenic enzymes, CYP17 and CYP19.

29 able to better discriminate with respect to CYP17 and CYP19.

30 ever, no mutations have been reported in the CYP17 and CYP21 genes, which encode these P450 enzymes.

31 n two genes involved in estrogen metabolism, CYP17 and HSD17B1, were useful in developing a breast ca

32 sed the association between the A2 allele of CYP17 and invasive endometrial cancer risk in a case-con

33 These cells also express Cyp17 and respond to hCG stimulation but do not express

34 ruitment, and induces the mRNA expression of CYP17 and several other steroidogenic genes.

35 restriction sites for MspAI (A2 polymorphism-CYP17) and NlaIII (Val/Met polymorphism-COMT).

36 ce, resulted in the up-regulation of cyp11a, cyp17, and 3beta-hsd and the down-regulation of cyp19a.

37 Furthermore, selectivities over CYP11B2, CYP17, and CYP19 were observed, as well as satisfying me

38 ediated down-regulation of the expression of Cyp17, and perhaps P450scc, contributes to that effect.

39 Possession of the A2 variant of CYP17 appears to increase risk for ovarian cancer, where

40 mutant luteinized theca cells overexpressing CYP17 are common in ovarian cancer stroma.

41 sterone production through the inhibition of Cyp17 as previously described, to directly reducing both

42 ity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxylase activity.

43 Human cytochrome P450 17alpha-hydroxylase (CYP17) catalyses not only the 17alpha-hydroxlation of pr

44 Cytochrome P450c17 (CYP17) catalyzes both the 17alpha-hydroxylase and 17,20-

45 Disabling mutations in CYP17 cause combined 17alpha-hydroxylase/17,20-lyase def

46 Baboon and human CYP17 cDNA share 96% homology.

47 ried or was homozygous for the A2 variant of CYP17 compared with 53.9% of controls, for a RR (and 95%

48 Cytochrome p450c17 (CYP17) converts the C21 steroids pregnenolone and proges

49 Thus, CYP17 CRS1 is a transcriptional regulatory element conta

50 Dual CYP17/CYP11B2 inhibitors are proposed as a novel strateg

51 nM) and selectivity over CYP11B1 (SF = 422), CYP17, CYP19, and a panel of hepatic CYP enzymes.

52 These data suggest that the A2 allele of CYP17 decreases endometrial cancer risk, but has only we

53 allele of the cytochrome P450c17alpha gene (CYP17), designated A2.

54 were shown to be potent inhibitors of human CYP17 enzyme as well as potent antagonist of both wild t

55 features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipH

56 to high inhibitory potency against the human CYP17 enzyme.

57 d that the 17,20-lyase activities of Xenopus CYP17 exceeded the 17alpha-hydroxylase activities in bot

58 The kinetics of Xenopus CYP17 expressed in yeast microsomes were therefore exami

59 Androgen receptor (AR) and CYP17 expression were assessed by immunohistochemistry,

60 sses whereas mutant GT198 protein stimulates CYP17 expression.

61 s remarkably robust activity exceeds that of CYP17 from most higher vertebrates, and likely explains

62 after expressing recombinant DNAs, encoding CYP17 from various species, in nonsteroidogenic mammalia

63 epressor that regulates transcription of the CYP17 gene by periodically interacting with steroidogeni

64 eneral control nonderepressed 5) and repress CYP17 gene expression.

65 SF1 and inhibits cyclic AMP (cAMP)-dependent CYP17 gene transcription.

66 y to determine whether a polymorphism in the CYP17 gene was associated with risk of breast cancer.

67 ated for ever use versus never use of ERT by CYP17 genotype (TT, TC, and CC).

68 previously examined the relationship between CYP17 genotype and circulating hormone levels (total n =

69 we further examined the relationship between CYP17 genotype and endogenous plasma steroid hormone lev

70 We also evaluated associations between this CYP17 genotype and plasma steroid hormone levels among p

71 We now show that CYP17 genotype is associated with serum hormone levels a

72 These findings suggest that the CYP17 genotype may be a biomarker for the onset of ovula

73 sk and estrogen replacement therapy (ERT) by CYP17 genotype using 51 incident cases and 391 randomly

74 ther endometrial cancer risk associated with CYP17 genotype was modified by established endometrial c

75 romotes aggression and dominance, and ar and cyp17 (gonad) were elevated in nonexposed males paired w

76 Baboon CYP17 had a significantly higher activity for progestero

77 Baboon CYP17 has apparent Km and V values for pregnenolone and

78 Among women, the A2 allele of CYP17 has been associated with elevated levels of endoge

79 The A2 allele of CYP17 has been associated with polycystic ovarian syndro

80 nd higher primate adrenals secrete steroids, CYP17 has been characterized in the Cape baboon, a speci

81 cAMP-responsive sequence (CRS1) from bovine CYP17 has previously been shown to be a binding site for

82 , in the transcriptional activation of human CYP17 (hCYP17) in H295R human adrenocortical cells is es

83 sex steroid production/signaling (cyp19a1b, cyp17, hsd11b2, hsd17b3, ar) and aggression (avplrv1b, t

84 Testicular Cyp17 hydroxylase and lyase activities were also signifi

85 rationale for and implications of targeting CYP17 in CRPC and focus on established and novel CYP17 i

86 an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resi

87 is increase in PA concentrations facilitates CYP17 induction.

88 is supported by the clinical efficacy of the CYP17 inhibitor abiraterone.

89 ne acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/d

90 l agent (an inhibitor of androgen synthesis (CYP17 inhibitor)/antiandrogen) that is significantly mor

91 abiraterone acetate, an orally administered CYP17 inhibitor, which suppresses androgen synthesis has

92 Conformational profiling revealed that the CYP17 inhibitor-bound AR adopted a conformation that res

93 Recently, however, it has been reported that CYP17 inhibitors can interact directly with the androgen

94 ts of this study suggest that the ability of CYP17 inhibitors to directly antagonize the AR may contr

95 The most potent CYP17 inhibitors were 3beta-hydroxy-17-(1H-benzimidazole

96 ent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts w

97 nd-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with non

98 7 in CRPC and focus on established and novel CYP17 inhibitors, including ketoconazole, abiraterone ac

99 Here, we have demonstrated that CYP17 inhibitors, with the exception of orteronel, can f

100 acophore model in identifying new and potent CYP17 inhibitors.

101 inding requirements for two classes of human CYP17 inhibitors.

102 The steroidogenic enzyme CYP17 is responsible for catalyzing the production of an

103 CYP17 is transcribed at developmental stages and in brai

104 tion, and in situ hybridization to show that CYP17 is transcribed in developing and adult brains.

105 del for the P450 enzyme cytochrome P450 C17 (CYP17) is presented based on sequence alignments of mult

106 CYP17 isoforms generally rely on the cofactor cytochrome

107 Most mammalian CYP17 isoforms have high 17alpha-hydroxylase relative to

108 study recently reported that seviteronel, a CYP17 lyase-selective inhibitor, aedemonstrated a sustai

109 CYP17 may therefore have evolved from a general producer

110 osynthesis of androgens in CRPC by targeting CYP17 may thus represent a rational therapeutic approach

111 Xenopus CYP17 mediated both 17,20-lyase reactions in the absence

112 only the human b(5) cofactor enhanced human CYP17-mediated lyase activity, implying that the human e

113 pus and human b(5) slightly enhanced Xenopus CYP17-mediated lyase activity, indicating that the enzym

114 ting that the high lyase activity of Xenopus CYP17 might be due to a lesser dependence on b(5).

115 These data suggest that the A2 allele of CYP17 modifies endogenous hormone levels, but is not a s

116 The CYP17 molecule in this model is in the form of a triangu

117 ve in situ hybridization, we measured higher CYP17 mRNA levels in the POA of PostOv lizards compared

118 ias, and gynecomastia, who is homozygous for CYP17 mutation E305G, which lies in the active site.

119 C(50 CYP11B1)/IC(50 CYP11B2)) around 50) and CYP17 (no inhibition).

120 17-heteroarylsteroid (17-HAS) inhibitors of Cyp17, one of the rate-limiting enzymes in the biosynthe

121 These preliminary findings suggest that CYP17 or other variants in estrogen biosynthesis or meta

122 In contrast, Xenopus laevis CYP17 potently regulates all four reactions in the frog

123 The enzyme CYP17 primarily regulates androgen production by mediati

124 amino acid residues between human and baboon CYP17, primarily in helices F and G and the F-G loop.

125 The chromatin-bound GT198 on the human CYP17 promoter is decreased by overexpressing mutant GT1

126 ctivity attenuates the binding of SF1 to the CYP17 promoter, and silencing of DGK-theta expression in

127 but had no effect on a 17alpha-hydroxylase (CYP17) promoter construct.

128 The levels of phosphorylated IRS1 and CYP17 protein were higher in the ovary of DIO-WT compare

129 he Delta4 and Delta5 pathways; thus, Xenopus CYP17 rapidly converted pregnenolone and progesterone to

130 PA stimulates SF1-dependent transcription of CYP17 reporter plasmids, promotes coactivator recruitmen

131 s and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERbeta rs1256049, ERbet

132 creased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modu

133 orts to understand the complex enzymology of CYP17, structure/function relationships have been report

134 ch could be involved in a hydrogen bond with CYP17 substrates and the shape and location of a cavity.

135 stenedione in isolated oocytes by the enzyme CYP17, suggesting that androgens may be promoting matura

136 ncer was higher for women homozygous for the CYP17 T allele (OR, 4.10; 95% CI, 1.64-10.3), but not fo

137 t pathway to C19 steroids catalyzed by human CYP17 (the delta5-steroid pathway).

138 pression of 17alpha-hydroxylase/17,20 lyase (CYP17), the enzyme that synthesizes the androgenic subst

139 hibitors of 17alpha-hydroxylase/17,20-lyase (CYP17), the key enzyme which catalyzes the biosynthesis

140 for the active site of human cytochrome P450 CYP17, the 3D structure of which is unknown.

141 rug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in an

142 nts homozygous for substitution mutations in CYP17, the gene encoding P450c17.

143 cortex, adrenocorticotropin (ACTH) activates CYP17 transcription by promoting the binding of the nucl

144 n CtBP protein partnering and ACTH-dependent CYP17 transcription.

145 ons modulate the ability of CtBP1 to repress CYP17 transcription.

146 DGK-theta expression inhibits cAMP-dependent CYP17 transcription.

147 Pretreatment CYP17 tumor expression >/= 10% was correlated with incre

148 lear expression of AR, combined with >/= 10% CYP17 tumor expression, was correlated with longer time

149 Women with the A2 allele of CYP17 were at decreased risk of endometrial cancer (A1/A

150 orphism in the cytochrome P450c17alpha gene (CYP17), which is associated with higher endogenous hormo

151 both MIS-treated rats and mice, the mRNA for Cyp17, which catalyzes the committed step in androgen sy

152 (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in th