Monash Institute of Pharmaceutical Sciences , Monash University , Parkville , Victoria 3052 , Australia.
Department of Pathology , Brigham and Women's Hospital , Boston , Massachusetts 02135 , United States.
J Med Chem. 2018 Sep 13;61(17):7448-7470. doi: 10.1021/acs.jmedchem.8b00318. Epub 2018 May 10.
Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.
早期药物发现针对相对较新或较难的靶点时，常常会出现命中筛选不足的情况。针对这些靶点的文献综述很少深入研究对相关筛选命中物进行严格分析所需的细节。在这里，我们以相对较难的靶点之一酶谷胱甘肽转移酶 ω-1（GSTO1-1）为例，对涉及小分子抑制剂的相关文献进行了综述。在这个过程中，我们特别关注了检测干扰和命中质量方面。我们相信，这一对该靶点抑制剂未来发展的观点将是一个有用的指南，同时也为新靶点或难靶点的未来综述格式提供了模板。
