WB2838 [3-氯-4-(2-氨基-3-氯苯基)-吡咯]：一种由假单胞菌产生的非甾体雄激素受体拮抗剂。

WB2838 [3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole]: non-steroidal androgen-receptor antagonist produced by a Pseudomonas.

作者信息

Hori Y, Abe Y, Nakajima H, Takase S, Fujita T, Goto T, Okuhara M, Kohsaka M

机构信息

Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.

出版信息

J Antibiot (Tokyo). 1993 Sep;46(9):1327-33. doi: 10.7164/antibiotics.46.1327.

DOI:10.7164/antibiotics.46.1327

PMID:8226310

Abstract

In the course of our search for non-steroidal androgen-receptor antagonists of microbial origin, Pseudomonas sp. No. 2838 was found to produce an inhibitor of androgen binding to its receptor. This compound, named WB2838, was isolated and identified as 3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole. The IC50 value of WB2838 for partially purified rat prostate cytosol receptor was 8.0 x 10(-7) M. However, the IC50 value of WB2838 against estrogen-receptor binding was about 90-fold greater than that against androgen-receptor binding. WB2838 inhibited the growth of androgen-responsive mouse mammary carcinoma SC-3 cells in the presence of 10(-8) M testosterone at IC50 value of 4.1 x 10(-7) M. This inhibition was reversed by adding 10(-5) M testosterone to the culture medium. WB2838 also showed the inhibitory activity against the growth of the ventral prostate induced by testosterone propionate in castrated immature rats. Therefore, it was concluded that WB2838 was a non-steroidal androgen-receptor antagonist.

摘要

在我们寻找微生物来源的非甾体雄激素受体拮抗剂的过程中，发现假单胞菌属2838号菌株能产生一种雄激素与其受体结合的抑制剂。这种化合物名为WB2838，已被分离并鉴定为3-氯-4-(2-氨基-3-氯苯基)-吡咯。WB2838对部分纯化的大鼠前列腺胞质溶胶受体的IC50值为8.0×10⁻⁷ M。然而，WB2838对雌激素受体结合的IC50值比对雄激素受体结合的IC50值大约高90倍。在存在10⁻⁸ M睾酮的情况下，WB2838以4.1×10⁻⁷ M的IC50值抑制雄激素反应性小鼠乳腺癌SC-3细胞的生长。向培养基中添加10⁻⁵ M睾酮可逆转这种抑制作用。WB2838还显示出对丙酸睾酮诱导的去势未成熟大鼠腹侧前列腺生长的抑制活性。因此，得出结论，WB2838是一种非甾体雄激素受体拮抗剂。