Antiandrogens: selective androgen receptor modulators
Antiandrogens: selective androgen receptor modulators
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DOI：
10.1016/s0303-7207(02)00373-8
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发表时间：
2002-12-30
影响因子：
4.1
通讯作者：
Brinkmann, AO
中科院分区：
文献类型：
--
作者：
Berrevoets, CA;Umar, A;Brinkmann, AO
抗雄激素药物能有效阻断雄激素受体（AR）介导的基因表达，因此是治疗雄激素依赖性前列腺癌的有效工具。抗雄激素是AR活性的完全或部分抑制剂，这取决于化合物的性质。与雄激素相比，抗雄激素诱导不同的AR构象，从而影响辅调节因子（辅激活因子和辅抑制因子）的募集。这种AR活性的配体选择性调节受前列腺癌中发现的AR突变（Thr877Ala取代）的影响。与野生型AR相反，由醋酸环丙孕酮（CPA）和羟基芴醇（OHF）诱导的突变体AR构象与雄激素诱导的构象相当。因此，这可能影响共调节因子的募集，从而允许CPA和OHF作为突变体AR的强激动剂。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Antiandrogens can efficiently block androgen receptor (AR) mediated gene expression, and are therefore useful tools in the treatment of androgen dependent prostate cancer. Antiandrogens are either complete or partial inhibitors of AR activity, depending on the nature of the compound. As compared to androgens, antiandrogens induce a different AR conformation, thereby influencing the recruitment of co-regulators (coactivators and corepressors). This ligand-selective modulation of AR activty is affected by an AR mutation (Thr877Ala substitution) found in prostate cancer. In contrast to the wild-type AR, the mutant AR conformation induced by cyproterone acetate (CPA) and hydroxyflutamide (OHF) is comparable to that induced by androgens. As a consequence, this might affect recruitment of co-regulators, thereby allowing CPA and OHF to act as strong agonists on the mutant AR. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.