From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems

Molecules

Sascha Hoogendoorn¹  IoannisA. Tsakoumagkos¹  QuentinT. L. Pasquer¹ 

[1] Department of Organic Chemistry, University of Geneva, Quai Ernest-Ansermet 30, 1211 Genève, Switzerland;

关键词: phenotypic screening;    target identification;    mechanism of action;    drug discovery;    chemical probes;    photo-affinity labeling;   

DOI  :  10.3390/molecules25235702

来源: DOAJ

【 摘 要 】

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.

【 授权许可】

Unknown