前列腺癌是最常見的男性泌尿生殖系統(tǒng)的惡性腫瘤。雄激素受體在前列腺癌的發(fā)生、發(fā)展中起著重要作用。目前,所有治療前列腺癌的藥物(包括第一代的氟他胺、比卡魯胺、尼魯米特和第二代的恩扎魯胺)都與雄激素受體的配體結(jié)合口袋結(jié)合,并且這些藥物有著相似的分子結(jié)構(gòu),這可能引起藥物之間的交叉耐藥。為了避免耐藥性的產(chǎn)生,研究者們致力于發(fā)現(xiàn)雄激素受體上新的藥物結(jié)合位點(diǎn)。除雄激素受體配體結(jié)合位點(diǎn)外,主要對(duì)作用于氮端結(jié)合位點(diǎn)上的第一活性功能區(qū)(AF1)、第二活性功能區(qū)(AF2)、AF2附近的第三結(jié)合功能區(qū)(BF3)和DNA結(jié)合位點(diǎn)(DBD)的藥物進(jìn)行綜述。

Prostate cancer is the most common malignant tumor of male urogenital system. The androgen receptor plays an important role in the occurrence and progression of prostate cancer. So far, all prostate cancer drugs including the first generation anti-androgens flutamide, bicalutamide, nilutamide, and the second generation enzalutamide, are combined with androgen receptor ligand binding pocket. In addition, they share a similar molecular scaffold which increases the likelihood of cross resistance. Accordingly, alternative sites of the androgen receptor have been attempted to overcome resistance to these anti-androgens. Besides ligand binding domain, prostate cancer drugs targeting active function 1 (AF1) in N-terminal domain, active function 2 (AF2), binding function 3 (BF3) near AF2, and DNA binding domain (DBD) are reviewed.