Chemoproteomic discovery of a covalent allosteric inhibitor of WRN helicase.
Baltgalvis KA, Lamb KN, Symons KT, Wu CC, Hoffman MA, Snead AN, Song X, Glaza T, Kikuchi S, Green JC, Rogness DC, Lam B, Rodriguez-Aguirre ME, Woody DR, Eissler CL, Rodiles S, Negron SM, Bernard SM, Tran E, Pollock J, Tabatabaei A, Contreras V, Williams HN, Pastuszka MK, Sigler JJ, Pettazzoni P, Rudolph MG, Classen M, Brugger D, Claiborne C, Plancher JM, Cuartas I, Seoane J, Burgess LE, Abraham RT, Weinstein DS, Simon GM, Patricelli MP, Kinsella TM.
Baltgalvis KA, et al.
Nature. 2024 May;629(8011):435-442. doi: 10.1038/s41586-024-07318-y. Epub 2024 Apr 24.
Nature. 2024.
PMID: 38658751
VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary for proper helicase function, resulting in widespread double-stranded DNA breaks, nuclear swelling and cell death in MSI-high (MSI-H), …
VVD-133214 binds WRN protein cooperatively with nucleotide and stabilizes compact conformations lacking the dynamic flexibility necessary fo …