Department of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, James Clerk Maxwell Building, 57 Waterloo Road, London, SE1 8WA, UK.
School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Eur J Pharmacol. 2023 Oct 5;956:175953. doi: 10.1016/j.ejphar.2023.175953. Epub 2023 Aug 2.
Liver X receptors (LXRs) are master regulators of various biological processes, including metabolism, inflammation, development, and reproduction. As well-known nuclear oxysterol receptors of the nuclear receptor (NR) family, LXRs have two homologous subtypes, LXRα (NR1H3) and LXRβ (NR1H2). Since the mid-1990s, numerous LXR-targeted drugs have been designed to treat diseases such as atherosclerosis, systemic lupus erythematosus, and cancer. These modulators include agonists and antagonists, and the selectivity of them have been development from diverse aspects, including subtype-specific, cell-specific, tissue-specific types. Meanwhile, advanced delivery systems are also exploreed to facilitate the application of LXR drugs in clinical setting. One of the most promising delivery systems involves the use of nanoparticles and is expected to increase the clinical potential of LXR modulators. This review discusses our current understanding of LXR biology and pharmacology, focusing on the development of modulators for LXRα and/or LXRβ, and the nanoparticle-based delivery systems for promising LXR modulators with potential for use as drugs.
肝 X 受体 (LXRs) 是多种生物学过程的主要调节剂，包括代谢、炎症、发育和生殖。作为核受体 (NR) 家族中众所周知的核甾醇受体，LXR 有两个同源亚型，LXRα (NR1H3) 和 LXRβ (NR1H2)。自 20 世纪 90 年代中期以来，已经设计了许多针对 LXR 的药物来治疗动脉粥样硬化、系统性红斑狼疮和癌症等疾病。这些调节剂包括激动剂和拮抗剂，它们的选择性已经从多个方面得到了发展，包括亚型特异性、细胞特异性、组织特异性。同时，也在探索先进的给药系统，以促进 LXR 药物在临床环境中的应用。最有前途的给药系统之一涉及使用纳米粒子，有望增加 LXR 调节剂的临床潜力。本文综述了我们对 LXR 生物学和药理学的现有认识，重点介绍了针对 LXRα 和/或 LXRβ 的调节剂的开发，以及具有作为药物应用潜力的基于纳米粒子的有前途的 LXR 调节剂的给药系统。
