Combining experimental strategies for successful target deconvolution.
Wilkinson IVL., Terstappen GC., Russell AJ.
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.