Kristen A Baltgalvis, Kelsey N Lamb, Kent T Symons, Chu-Chiao Wu, Melissa A Hoffman, Aaron N Snead, Xiaodan Song, Thomas Glaza, Shota Kikuchi, Jason C Green, Donald C Rogness, Betty Lam, Maria E Rodriguez-Aguirre, David R Woody, Christie L Eissler, Socorro Rodiles, Seth M Negron, Steffen M Bernard, Eileen Tran, Jonathan Pollock, Ali Tabatabaei, Victor Contreras, Heather N Williams, Martha K Pastuszka, John J Sigler, Piergiorgio Pettazzoni, Markus G Rudolph, Moritz Classen, Doris Brugger, Christopher Claiborne, Jean-Marc Plancher, Isabel Cuartas, Joan Seoane, Laurence E Burgess, Robert T Abraham, David S Weinstein, Gabriel M Simon, Matthew P Patricelli, Todd M Kinsella
WRN helicase is a promising target for treatment of cancers with microsatellite instability (MSI) due to its essential role in resolving deleterious non-canonical DNA structures that accumulate in cells with faulty mismatch repair mechanisms1-5 . Currently there are no approved drugs directly targeting human DNA or RNA helicases, in part owing to the challenging nature of developing potent and selective compounds to this class of proteins. Here we describe the chemoproteomics-enabled discovery of a clinical-stage, covalent allosteric inhibitor of WRN, VVD-133214...
April 24, 2024: Nature