Document Report Card

ID: ALA1140283

Journal: J Med Chem

Title: Novel, potent small-molecule inhibitors of the molecular chaperone Hsp90 discovered through structure-based design.

Authors: Dymock BW, Barril X, Brough PA, Cansfield JE, Massey A, McDonald E, Hubbard RE, Surgenor A, Roughley SD, Webb P, Workman P, Wright L, Drysdale MJ.

Abstract: The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmacodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

CiteXplore: 15974572

DOI: 10.1021/jm050355z