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Design, synthesis, and biological evaluation of conformationally constrained cis-amide Hsp90 inhibitors.

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.

SUBMITTER: Duerfeldt AS

PROVIDER: S-EPMC2697668 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Design, synthesis, and biological evaluation of conformationally constrained cis-amide Hsp90 inhibitors.

Duerfeldt Adam S AS Brandt Gary E L GE Blagg Brian S J BS

Organic letters 20090601 11

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. ...[more]

PMID: 19435295

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