Author/Authors :
Thomas E. Barta، نويسنده , , James M. Veal، نويسنده , , John W. Rice، نويسنده , , Jeffrey M. Partridge، نويسنده , , R. Patrick Fadden، نويسنده , , Wei Ma، نويسنده , , Matthew Jenks، نويسنده , , Lifeng Geng، نويسنده , , Gunnar J. Hanson، نويسنده , , Kenneth H. Huang، نويسنده , , Amy F. Barabasz، نويسنده , , Briana E. Foley، نويسنده , , James Otto، نويسنده , , Steven E. Hall، نويسنده ,
Abstract :
Hsp90 maintains the conformational stability of multiple proteins implicated in oncogenesis and has emerged as a target for chemotherapy. We report here the discovery of a novel small molecule scaffold that inhibits Hsp90. X-ray data show that the scaffold binds competitively at the ATP site on Hsp90. Cellular proliferation and client assays demonstrate that members of the series are able to inhibit Hsp90 at nanomolar concentrations.
Keywords :
Benzamide , Hsp70 , Carbazol-4-one , HSP90 , Cancer therapeutic , Heat shock protein 90 , X-ray structure , ATP , HER2 , Cancer inhibitor
