ライフサイエンスコーパス: AKR1C3

1 dently activated by aldo-keto-reductase 1C3 (AKR1C3).

2 receptors belong to the AKR1C family (AKR1C1-AKR1C3).

3 ounted by indomethacin a potent inhibitor of AKR1C3.

4 This makes AKR1C3 a target for the treatment of CRPC.

5 (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate

6 These results suggest that AKR1C3 activation is a critical resistance mechanism ass

7 -vivo and in-vitro evidence of modulation of AKR1C3 activity by insulin in PCOS and in women with INS

8 ve adipose androgen generation by increasing AKR1C3 activity in female subcutaneous adipose tissue.

9 Here we assessed the effect of insulin on AKR1C3 activity in vivo and in vitro.

10 AKR1C3 and AKR1C1 were localized on the same myoepitheli

11 phase II inducers but not the highly related AKR1C3 and AKR1C4 family members (84% sequence homology)

12 sed to inhibit cyclooxygenase, also inhibits AKR1C3 and displays selectivity over AKR1C1/AKR1C2.

13 cant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT.

14 Homogeneous recombinant AKR1C1, AKR1C3, and AKR1C4 gave similar catalytic profiles to th

15 mes involved in androgen synthesis (CYP17A1, AKR1C3, and HSD17B6), as well as expression of full-leng

16 D5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization

17 Inhibition of AKR1C3 by indomethacin, a nonsteroidal anti-inflammatory

18 lation of cellular stress markers AKR1C2 and AKR1C3 can be quantitatively measured in the presence of

19 We further found that AKR1C3 can bind Siah2 and inhibit its self-ubiquitinatio

20 roduction of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line.

21 and blocked testosterone formation in LNCaP-AKR1C3 cells.

22 mediated production of testosterone in LNCaP-AKR1C3 cells.

23 In contrast, overexpression of AKR1C3 confers resistance to enzalutamide.

24 roid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3) converts Delta(4)-androstene-3,17-dione and 5alp

25 rison with those of AKR1C1 and AKR1C2, PGFS (AKR1C3) could catalyze the reduction and/or oxidation re

26 progesterone-related genes (AKR1C1, AKR1C2, AKR1C3, CYP3A4, SRD5A1, SRD5A2, and PGR) influenced brea

27 1C1 and, to a lesser extent, AKR1C2 (but not AKR1C3) decreased progesterone-dependent PR activation o

28 To investigate the functional role of AKR1C3 during PHK differentiation, its expression and ac

29 AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized e

30 in CWR22Rv1 prostate cancer cells decreased AKR1C3 expression as well as intracellular androgen leve

31 Knockdown of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzym

32 AKR1C3 expression correlated positively with body-mass i

33 rapy for relapsed/refractory T-ALL, and that AKR1C3 expression could be used as a biomarker to select

34 PHKs, we used immunofluorescence to examine AKR1C3 expression in AD and psoriasis lesions.

35 Insulin significantly increased AKR1C3 expression in differentiated subcutaneous adipocy

36 AD-associated mediator, PGD(2), upregulated AKR1C3 expression in PHKs, we used immunofluorescence to

37 analysis and quantitative PCR confirmed that AKR1C3 expression was also upregulated in differentiatio

38 AKR1C3 expression was measured by real-time PCR.

39 vitro, and that sensitivity correlated with AKR1C3 expression.

40 hibition of AR activity by itself stimulated AKR1C3 expression.

41 Aldo-keto reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex

42 Overexpression of AKR1C3 in a resistant BCP-ALL xenograft resulted in dram

43 Our work demonstrates a function for AKR1C3 in differentiation-associated gene regulation and

44 We observed parallel expression of Siah2 and AKR1C3 in human prostate cancer tissues.

45 he inducible aldo-keto reductases AKR1C2 and AKR1C3 in living human cells.

46 ght to investigate the expression pattern of AKR1C3 in normal human epidermis.

47 tively, our findings identify a new role for AKR1C3 in regulating Siah2 stability and thus enhancing

48 fluorescence revealed a strong expression of AKR1C3 in the differentiated suprabasal layers compared

49 wn cells, suggesting a nonenzymatic role for AKR1C3 in these outcomes.

50 ostenedione through aldoketoredutase type 3 (AKR1C3) in women with insulin resistance.

51 Selective AKR1C3 inhibition might offer a novel therapeutic target

52 s on the phenylamino B-ring were optimal for AKR1C3 inhibition.

53 replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that displays selectivity for AKR1C3 ov

54 Selective AKR1C3 inhibitors are required because compounds should

55 Two of the best selective AKR1C3 inhibitors had K(i) values of 0.1 and 2.7 muM, ex

56 AKR1C3 inhibitors should not inhibit AKR1C1/AKR1C2, whic

57 s in particular, are potent but nonselective AKR1C3 inhibitors.

58 yclooxygenase inhibitory activity but retain AKR1C3 inhibitory potency and selectivity.

59 analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity.

60 The aim of this study was to test whether AKR1C3 is a predictive biomarker of in vivo PR-104 sensi

61 In addition, AKR1C3 is highly expressed in metastatic and recurrent p

62 In CRPC, AKR1C3 is implicated in drug resistance, and enzalutamid

63 AKR1C3 is upregulated in CRPC where it catalyzes the for

64 cells elevated Siah2 protein levels, whereas AKR1C3 knockdown had the opposite effect.

65 ibitory activity on COX isozymes and blocked AKR1C3 mediated production of T and induction of PSA in

66 d not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1

67 llular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate,

68 AKR1C3 mRNA expression was significantly higher in subcu

69 The AKR1C3.NADP(+).2'-des-methyl-indomethacin crystal struct

70 covered with low muM K(i) values for AKR1C1, AKR1C3, or both.

71 R1C3 inhibitor that displays selectivity for AKR1C3 over other AKR1C enzymes.

72 wild-type or catalytically inactive forms of AKR1C3 partially rescued AR activity and growth defects

73 Unexpectedly, AKR1C3 re-expression in Siah2 knockdown cells elevated S

74 p relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electr

75 vely the formation of 3beta-hydroxytibolone, AKR1C3 showed weak 3beta/3alpha-HSD activity, and AKR1C4

76 ereas 17beta-hydroxysteroid dehydrogenase 5 (AKR1C3) showed predominance in SC adipose tissue.

77 genes mediating androgen metabolism (HSD3B2, AKR1C3, SRD5A1, AKR1C2, AKR1C1, and UGT2B15).

78 in aldo-keto reductase family 1, member C3 (AKR1C3), the prostatic enzyme that reduces adrenal andro

79 For rs12387 in AKR1C3, the presence of 1 or 2 G alleles was associated

80 criptase-PCR showed that AKR1C1, AKR1C2, and AKR1C3 transcripts were all expressed.

81 Aldo-keto reductase 1C3 (AKR1C3; type 5 17beta-hydroxysteroid dehydrogenase) is o

82 AKR1C3 was found to be upregulated in AD but not in psor

83 Expression of AKR1C3 was significantly higher in T-ALL xenografts comp

84 One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide-resis

85 somerase mRNA expression, but express AKR1C1-AKR1C3) were able to convert DHT into 3alpha- and 3beta-

86 transfected with AKR1C1 and AKR1C2, but not AKR1C3, were able to significantly inhibit a dose-depend

87 genic enzymes, including SRD5A1, SRD5A3, and AKR1C3, whereas expression of SRD5A2, CYP3A4, CYP3A5, an

88 , ligand access to PPARgamma is regulated by AKR1C3, which diverts PGD(2) metabolism away from J-seri

89 genes we found to be regulated by Siah2 was AKR1C3, which encodes a key androgen biosynthetic enzyme

90 In contrast, AKR1C3, which shares 84% sequence identity, and 5alpha-r

91 sistance; targeting intracrine androgens and AKR1C3 will overcome enzalutamide resistance and improve

92 The lead compounds inhibited AKR1C3 with nanomolar potency, displayed >100-fold selec

93 ased on 7 landscape genes (POLD2, CYCS, MYC, AKR1C3, YME1L1, ANXA7, and PDCD4) is associated with the