Levine Paul M, Garabedian Michael J, Kirshenbaum Kent
Department of Chemistry, New York University , New York, New York 10003, United States.
J Med Chem. 2014 Oct 23;57(20):8224-37. doi: 10.1021/jm500101h. Epub 2014 Jul 8.
The androgen receptor (AR) is a major therapeutic target in prostate cancer pharmacology. Progression of prostate cancer has been linked to elevated expression of AR in malignant tissue, suggesting that AR plays a central role in prostate cancer cell biology. Potent therapeutic agents can be precisely crafted to specifically target AR, potentially averting systemic toxicities associated with nonspecific chemotherapies. In this review, we describe various strategies to generate steroid conjugates that can selectively engage AR with high potency. Analogies to recent developments in nonsteroidal conjugates targeting AR are also evaluated. Particular focus is placed on potential applications in AR pharmacology. The review culminates with a description of future prospects for targeting AR.
雄激素受体（AR）是前列腺癌药理学中的主要治疗靶点。前列腺癌的进展与恶性组织中AR表达升高有关，这表明AR在前列腺癌细胞生物学中起核心作用。强效治疗剂可以精确设计以特异性靶向AR，从而可能避免与非特异性化疗相关的全身毒性。在本综述中，我们描述了生成能够高效选择性结合AR的甾体缀合物的各种策略。还评估了与靶向AR的非甾体缀合物的最新进展的类比。特别关注在AR药理学中的潜在应用。综述最后描述了靶向AR的未来前景。
