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Updated: Jun 23, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Design, synthesis, and biological evaluation of conformationally constrained cis-amide Hsp90 inhibitors
Adam S Duerfeldt1, Gary E L Brandt, Brian S J Blagg
1Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045-7562, USA.
Abstract:
Conformationally constrained cis-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.

