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

  • J Med Chem. 2005 Jun 30;48(13):4212-5. doi: 10.1021/jm050355z.
Brian W Dymock  1 ,  Xavier Barril ,  Paul A Brough ,  Julie E Cansfield ,  Andrew Massey ,  Edward McDonald ,  Roderick E Hubbard ,  Allan Surgenor ,  Stephen D Roughley ,  Paul Webb ,  Paul Workman ,  Lisa Wright ,  Martin J Drysdale
Affiliations
  • 1. Vernalis Ltd., Granta Park, Great Abington, Cambridge, UK.
PMID: 15974572 DOI: 10.1021/jm050355z
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.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15986
    VER-49009
    99.45%, HSP Inhibitor
    target: HSP
    Research Areas: Cancer