Discovery Biology, Eskitis Institute for Drug Discovery, Griffith University , Nathan, Queensland, Australia.
J Med Chem. 2013 Oct 24;56(20):7727-40. doi: 10.1021/jm4004279. Epub 2013 Aug 20.
Determining the activity of a compound and the potential impact on a diseased state is frequently undertaken using phenotypic or target-based approaches. Phenotypic screens have the advantage of the whole organism being exposed to the compound and thus all the targets and biological pathways associated with it. Cell penetration and access to targets in their "natural" environment are taken into account. Unless utilizing a genetically modified organism with an additional target associated indicator, elucidation of specific target(s) of active compounds is necessary. Target discovery is desirable to allow development of chemical entities based upon knowledge of the target structure. Phenotypic drug discovery has successfully identified new molecular entities for neglected protozoan disease research. In this perspective, the phenotypic approaches used to identify chemical entities for drug discovery and for use as tools against the parasites Plasmodium falciparum, Trypanosoma brucei brucei, and Trypanosoma cruzi will be outlined.
确定化合物的活性及其对疾病状态的潜在影响通常采用表型或基于靶标的方法进行。表型筛选具有整个生物体接触化合物的优势，因此考虑到与之相关的所有靶点和生物途径。细胞穿透和进入其“自然”环境中的靶点都被考虑在内。除非利用具有额外靶标相关指示物的遗传修饰生物体，否则有必要阐明活性化合物的特定靶标。靶标发现是必要的，以便能够基于靶标结构知识开发化学实体。表型药物发现已成功地为被忽视的原生动物病研究确定了新的分子实体。从这个角度来看，将概述用于发现药物的表型方法以及用于对抗疟原虫、布氏锥虫和克氏锥虫的寄生虫的工具。
