Department of Pharmacology and Physiology , Saint Louis University School of Medicine , St. Louis , Missouri 63104 , United States.
Chemistry Department, Faculty of Science , Benha University , Benha 13518 , Egypt.
J Med Chem. 2018 Dec 27;61(24):10935-10956. doi: 10.1021/acs.jmedchem.8b00045. Epub 2018 Jul 30.
Nuclear hormone receptors represent a large family of ligand-activated transcription factors that include steroid receptors, thyroid/retinoid receptors, and orphan receptors. Among nuclear hormone receptors, the liver X receptors have emerged as very important drug targets. These receptors regulate some of the most important metabolic functions, and they were also identified as anti-inflammatory transcription factors and regulators of the immune system. The development of drugs targeting liver X receptors continues to be a challenge, but advances in our knowledge of receptor structure and function move us forward, toward achieving this goal. This review highlights the latest advances in the development of synthetic LXR modulators in the primary literature from 2013 to 2017. In this review, we place great emphasis on the structure and function of LXRs because of their essential role in the drug design process. The structure-activity relationships of the most active and promising synthetic modulators are discussed.
核激素受体是一大类配体激活的转录因子家族，包括甾体激素受体、甲状腺/视黄酸受体和孤儿受体。在核激素受体中，肝 X 受体已成为非常重要的药物靶点。这些受体调节一些最重要的代谢功能，它们也被确定为抗炎转录因子和免疫系统的调节剂。针对肝 X 受体的药物开发仍然是一个挑战，但我们对受体结构和功能的认识的进步推动我们朝着实现这一目标前进。本综述重点介绍了 2013 年至 2017 年主要文献中合成 LXR 调节剂的最新进展。在本综述中，我们非常强调 LXR 的结构和功能，因为它们在药物设计过程中起着至关重要的作用。讨论了最活跃和最有前途的合成调节剂的构效关系。
