Hartmann Rolf W, Ehmer Peter B, Haidar Samer, Hector Markus, Jose Joachim, Klein Christian D P, Seidel Stefanie B, Sergejew Tom F, Wachall Bertil G, Wächter Gerald A, Zhuang Yan
Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany.
Arch Pharm (Weinheim). 2002 Apr;335(4):119-28. doi: 10.1002/1521-4184(200204)335:4<119::AID-ARDP119>3.0.CO;2-#.
Androgens are growth factors for approximately 80 percent of all prostate cancers. Suppressing androgen biosynthesis is therefore an important therapeutic strategy in order to inhibit tumor growth. Unfortunately, the drugs currently applied to lower androgen levels only affect testicular androgen production. Since androgens are also synthesized in the adrenal glands, tumor stimulation cannot be blocked completely. A new therapeutic target, CYP 17 (P450 17, 17alpha-hydroxylase-C17, C20 lyase), is likely to improve this situation. CYP 17 is a P450 enzyme and catalyzes the last step of androgen biosynthesis in both testes and adrenals. Inhibition of this enzyme will therefore result in a complete block of androgen production. This paper gives an overview of the current situation in this novel field of drug research and focuses on the development of steroidal and non-steroidal inhibitors of CYP 17.
雄激素是约80%的前列腺癌的生长因子。因此，抑制雄激素生物合成是抑制肿瘤生长的重要治疗策略。不幸的是，目前用于降低雄激素水平的药物仅影响睾丸雄激素的产生。由于肾上腺也能合成雄激素，所以无法完全阻断肿瘤刺激。一种新的治疗靶点——CYP 17（P450 17，17α-羟化酶-C17，C20裂解酶），有望改善这种情况。CYP 17是一种P450酶，催化睾丸和肾上腺中雄激素生物合成的最后一步。因此，抑制这种酶将导致雄激素产生的完全阻断。本文概述了这一药物研究新领域的现状，并着重介绍了CYP 17甾体和非甾体抑制剂的研发情况。
