Target deconvolution from phenotype-based drug discovery by using chemical proteomics approaches

Publication date: Available online 15 August 2018Source: Biochimica et Biophysica Acta (BBA) - Proteins and ProteomicsAuthor(s): Kazuishi Kubota, Masanori Funabashi, Yuji OguraAbstractPhenotype-based drug discovery is a key strategy for small molecule drug screening, and the molecular target identification of small molecules, termed “target deconvolution,” is critical albeit challenging. In this review, we classify approaches for target deconvolution, including both direct and indirect approaches, summarize their underlying principles, and provide examples of current chemical proteomics strategies including affinity purification using compound-immobilized beads, photoaffinity labeling (PAL), cellular thermal shift assay (CETSA), and activity-based protein profiling (ABPP). Because there is no single best target deconvolution strategy, it is important to carefully select a strategy on the basis of the test compound characteristics.

Source: Biochimica et Biophysica Acta (BBA) Proteins and Proteomics - August 15, 2018 Category: Biochemistry Source Type: research