Combining experimental strategies for successful target deconvolution

Isabel V L Wilkinson; Georg C Terstappen; Angela J Russell

doi:10.1016/j.drudis.2020.09.016

Combining experimental strategies for successful target deconvolution

Drug Discov Today. 2020 Sep 21:S1359-6446(20)30373-1. doi: 10.1016/j.drudis.2020.09.016. Online ahead of print.

Authors

Isabel V L Wilkinson¹, Georg C Terstappen², Angela J Russell³

Affiliations

¹ Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.
² Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3PQ, UK.
³ Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK; Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3PQ, UK. Electronic address: angela.russell@chem.ox.ac.uk.

PMID: 32971235
DOI: 10.1016/j.drudis.2020.09.016

Abstract

Investment in phenotypic drug discovery has led to increased demand for rapid and robust target deconvolution to aid successful drug development. Although methods for target identification and mechanism of action (MoA) discovery are flourishing, they typically lead to lists of putative targets. Validating which target(s) are involved in the therapeutic mechanism of a compound poses a significant challenge, requiring direct binding, target engagement, and functional studies in relevant physiological contexts. A combination of orthogonal approaches can allow target identification beyond the proteome as well as aid prioritisation for resource-intensive target validation studies.

Publication types

Review