McKenna Neil J
Department of Molecular and Cellular Biology and Nuclear Receptor Signaling Atlas Bioinformatics Resource, Baylor College of Medicine, Houston, Texas
Mol Pharmacol. 2016 Aug;90(2):153-9. doi: 10.1124/mol.116.103713. Epub 2016 May 23.
Nuclear receptor (NR) signaling pathways impact cellular function in a broad variety of tissues in both normal physiology and disease states. The complex tissue-specific biology of these pathways is an enduring impediment to the development of clinical NR small-molecule modulators that combine therapeutically desirable effects in specific target tissues with suppression of off-target effects in other tissues. Supporting the important primary research in this area is a variety of web-based resources that assist researchers in gaining an appreciation of the molecular determinants of the pharmacology of a NR pathway in a given tissue. In this study, selected representative examples of these tools are reviewed, along with discussions on how current and future generations of tools might optimally adapt to the future of NR signaling research.
核受体(NR)信号通路在正常生理和疾病状态下对多种组织的细胞功能产生影响。这些通路复杂的组织特异性生物学特性一直阻碍着临床NR小分子调节剂的开发,这类调节剂需要在特定靶组织中兼具治疗所需的效果,同时抑制其他组织中的脱靶效应。该领域的重要基础研究得到了多种基于网络的资源的支持,这些资源可帮助研究人员了解特定组织中NR信号通路药理学的分子决定因素。在本研究中,我们回顾了这些工具的选定代表性实例,并讨论了当前和未来几代工具如何能够最佳地适应NR信号研究的未来发展。