Bernhardt Rita
a Lehrstuhl für Biochemie , Universität des Saarlandes , Saarbrücken , Germany.
Expert Opin Ther Targets. 2016 Aug;20(8):923-34. doi: 10.1517/14728222.2016.1151873. Epub 2016 Mar 2.
Members of the CYP11B subfamily participate in the biosynthesis of important steroid hormones. CYP11B1 catalyzes the formation of cortisol, while CYP11B2 realizes the biosynthesis of aldosterone. Overproduction of cortisol is related to Cushing's disease, whereas overproduction of aldosterone leads to hypertension and end-organ damage such as cardiac and renal hypertrophy. Therefore, CYP11B1 and CYP11B2 have been defined as interesting targets for the development of novel drugs.
The paper describes the CYP11B1 and CYP11B2 genes and proteins, giving special attention to their functional and structural properties, the development of efficient test systems for potential inhibitors of both CYPs and the development and testing of novel potential drugs on the basis of selective inhibition of CYP11B1 and CYP11B2.
The availability of relevant and efficient screening systems for testing the effects of inhibitors of human CYP11B1 and CYP11B2, combined with experiences and success in synthesizing selective and efficient inhibitors of these isoenzymes, provides a realistic basis for a successful development of drugs using CYP11B1 and CYP11B2 as targets. The first clinical trials with the CYP11B2 inhibitor LCI699 demonstrated some side effects but showed inhibition of end-organ damage in animals, indicating that it might be a useful lead compound for future developments.
细胞色素P450 11B（CYP11B）亚家族成员参与重要甾体激素的生物合成。CYP11B1催化皮质醇的形成，而CYP11B2则实现醛固酮的生物合成。皮质醇过量产生与库欣病相关，而醛固酮过量产生会导致高血压和心脏及肾脏肥大等靶器官损害。因此，CYP11B1和CYP11B2已被确定为新型药物开发的有趣靶点。
本文描述了CYP11B1和CYP11B2基因及蛋白质，特别关注它们的功能和结构特性、针对这两种细胞色素P450潜在抑制剂的高效测试系统的开发以及基于对CYP11B1和CYP11B2的选择性抑制的新型潜在药物的开发与测试。
用于测试人CYP11B1和CYP11B2抑制剂效果的相关且高效的筛选系统的可用性，结合合成这些同工酶的选择性和高效抑制剂的经验与成功案例，为以CYP11B1和CYP11B2为靶点成功开发药物提供了现实基础。CYP11B2抑制剂LCI699的首次临床试验显示了一些副作用，但在动物实验中显示出对靶器官损害的抑制作用，表明它可能是未来药物开发的有用先导化合物。
