Tale of two WRN inhibitors: a covalent and a non-covalent molecule enter the clinic 

Since the discovery five years ago that WRN inhibition is synthetically lethal in microsatellite unstable cancers, two WRN inhibitors have advanced into Phase I trials, and at least four others are in preclinical development. With one of the clinical candidates a covalent inhibitor and the other non-covalent, their parallel development will enable comparison of the two approaches.

The two companies with clinical WRN inhibitors each published Nature papers on April 24, outlining their respective compound discovery methods. Both therapies are allosteric inhibitors that target the interface of the helicase domains, but one binds covalently and the other non-covalently. ...