Mikušová Katarína, Ekins Sean
Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia.
Collaborative Drug Discovery, Inc., 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA; Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA.
Drug Discov Today. 2017 Mar;22(3):534-545. doi: 10.1016/j.drudis.2016.09.025. Epub 2016 Oct 4.
Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project predominantly used phenotypic screening. From these projects we have examples of success (DprE1) and failure (PimA) going from drug to target and from target to drug, respectively. It is clear that we still have much to learn about the drug targets and the complex effects of the drugs on Mycobacterium tuberculosis. We propose a more integrated approach that learns from earlier drug discovery efforts that could help to move drug discovery forward.
近年来，结核病药物研发已从主要基于靶点的方法转向使用表型高通量筛选的方法。举例来说，通过我们由欧盟资助的第七框架计划合作项目，“结核病新药研发”是基于靶点的，而我们最近的“更多结核病药物”项目则主要使用表型筛选。从这些项目中，我们分别有从药物到靶点成功（DprE1）和从靶点到药物失败（PimA）的例子。显然，我们对于药物靶点以及药物对结核分枝杆菌的复杂作用仍有很多需要学习的地方。我们提出一种更综合的方法，借鉴早期药物研发的经验，这可能有助于推动药物研发的进展。
