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

Biochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):22-27. doi: 10.1016/j.bbapap.2018.08.002. Epub 2018 Aug 15.


Phenotype-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.

Keywords: Activity-based protein profile (ABPP); Cellular thermal shift assay (CETSA); Compound-immobilized beads; Phenotype-based drug discovery; Photoaffinity labeling (PAL); Target deconvolution.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods*
  • Drug Discovery / trends
  • Drug Evaluation, Preclinical / methods*
  • Drug Evaluation, Preclinical / trends
  • Humans
  • Phenotype
  • Photoaffinity Labels
  • Proteomics / methods*
  • Small Molecule Libraries


  • Photoaffinity Labels
  • Small Molecule Libraries