Chemical biology approaches targeting the actin cytoskeleton through phenotypic screening.

Chemical biology approaches targeting the actin cytoskeleton through phenotypic screening. Curr Opin Chem Biol. 2019 Mar 19;51:40-47 Authors: Bryce NS, Hardeman EC, Gunning PW, Lock JG Abstract The actin cytoskeleton is dysregulated in cancer, yet this critical cellular machinery has not translated as a druggable clinical target due to cardio-toxic side-effects. Many actin regulators are also considered undruggable, being structural proteins lacking clear functional sites suitable for targeted drug design. In this review, we discuss opportunities and challenges associated with drugging the actin cytoskeleton through its structural regulators, taking tropomyosins as a target example. In particular, we highlight emerging data acquisition and analysis trends driving phenotypic, imaging-based compound screening. Finally, we consider how the confluence of these trends is now bringing functionally integral machineries such as the actin cytoskeleton, and associated structural regulatory proteins, into an expanded repertoire of druggable targets with previously unexploited clinical potential. PMID: 30901618 [PubMed - as supplied by publisher]
Source: Current Opinion in Chemical Biology - Category: Biochemistry Authors: Tags: Curr Opin Chem Biol Source Type: research