Ligands of Therapeutic Utility for the Liver X Receptors.
Ligands of Therapeutic Utility for the Liver X Receptors.
复制标题
DOI：
10.3390/molecules22010088
复制
发表时间：
2017-01-05
期刊：
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Komati R;Spadoni D;Zheng S;Sridhar J;Riley KE;Wang G
肝X受体(LXRs)已被认为是一种潜在的治疗靶点，用于治疗从血管和代谢性疾病、神经退行性疾病到由脂质代谢驱动的癌症等一系列病理疾病。在加紧努力发现通过LXRs发挥作用的配体以实现令人垂涎的药理结果的同时，几种先导化合物已经在各种疾病干预的临床试验中进行测试。随着对小分子文库的筛选、合理的设计和经验药物化学方法的不断涌现，更有效和更有选择性的LXR配体不断涌现，但在最小化LXR激活对脂代谢的不良影响方面仍然存在挑战。本文对已知的内源性、天然和合成配体进行了综述。该综述还从分子模拟的角度提出了一些考虑，以便根据配体的相互作用能和β配体结合域中的重要氨基酸残基来设计更具体的LXRβ配体。
Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRβ ligands based on the interaction energies of ligands and the important amino acid residues in the LXRβ ligand binding domain.