Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU), 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Int J Mol Sci. 2020 Jul 31;21(15):5512. doi: 10.3390/ijms21155512.
Nuclear receptors are ligand-inducible transcriptional factors that control multiple biological phenomena, including proliferation, differentiation, reproduction, metabolism, and the maintenance of homeostasis. Members of the nuclear receptor superfamily have marked structural and functional similarities, and their domain functionalities and regulatory mechanisms have been well studied. Various modulators of nuclear receptors, including agonists and antagonists, have been developed as tools for elucidating nuclear receptor functions and also as drug candidates or lead compounds. Many assay systems are currently available to evaluate the modulation of nuclear receptor functions, and are useful as screening tools in the discovery and development of new modulators. In this review, we cover the chemical screening methods for nuclear receptor modulators, focusing on assay methods and chemical libraries for screening. We include some recent examples of the discovery of nuclear receptor modulators.
核受体是配体诱导的转录因子，可控制多种生物学现象，包括增殖、分化、繁殖、代谢和维持内稳态。核受体超家族的成员具有明显的结构和功能相似性，其结构域功能和调节机制已得到充分研究。各种核受体调节剂，包括激动剂和拮抗剂，已被开发为阐明核受体功能的工具，也被开发为候选药物或先导化合物。目前有许多用于评估核受体功能调节的测定系统，可作为新调节剂的发现和开发的筛选工具。在这篇综述中，我们涵盖了核受体调节剂的化学筛选方法，重点介绍了用于筛选的测定方法和化学文库。我们还包括一些核受体调节剂发现的最新实例。
