Tice Colin M, Noto Paul B, Fan Kristi Yi, Zhuang Linghang, Lala Deepak S, Singh Suresh B
Vitae Pharmaceuticals Inc. , 502 West Office Center Drive, Fort Washington, Pennsylvania 19034, United States.
J Med Chem. 2014 Sep 11;57(17):7182-205. doi: 10.1021/jm500442z. Epub 2014 May 28.
LXRs have been of interest as targets for the treatment of atherosclerosis for over a decade. In recent years, LXR modulators have also garnered interest for potential use in the treatment of inflammation, Alzheimer's disease (AD), dermatological conditions, hepatic steatosis, and oncology. To date, no LXR modulator has successfully progressed beyond phase I clinical trials. In this Perspective, we summarize published medicinal chemistry efforts in the context of the available crystallographic data, druglikeness, and isoform selectivity. In addition, we discuss the challenges that need to be overcome before an LXR modulator can reach clinical use.
十多年来，肝脏X受体（LXRs）一直是治疗动脉粥样硬化的热门靶点。近年来，LXR调节剂在治疗炎症、阿尔茨海默病（AD）、皮肤病、肝脂肪变性和肿瘤学方面的潜在用途也引起了关注。迄今为止，尚无LXR调节剂成功进入超过I期的临床试验。在本综述中，我们结合现有的晶体学数据、类药性质和亚型选择性，总结已发表的药物化学研究成果。此外，我们还讨论了LXR调节剂在进入临床应用之前需要克服的挑战。
