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Identification of a new scaffold for hsp90 C-terminal inhibition.

ABSTRACT: Inhibition of Hsp90 C-terminal function is an advantageous therapeutic paradigm for the treatment of cancer. Currently, the majority of Hsp90 C-terminal inhibitors are derived from novobiocin, a natural product traditionally used as an antibiotic. Assisted by molecular docking studies, a scaffold containing a biphenyl moiety in lieu of the coumarin ring system found in novobiocin was identified for development of new Hsp90 C-terminal inhibitors. Initial structure-activity studies led to derivatives that manifest good antiproliferative activity against two breast cancer cell lines through Hsp90 inhibition. This platform serves as a scaffold upon which new Hsp90 C-terminal inhibitors can be readily assembled for further investigation.

SUBMITTER: Zhao H

PROVIDER: S-EPMC4027776 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Identification of a new scaffold for hsp90 C-terminal inhibition.

Zhao Huiping H Moroni Elisabetta E Colombo Giorgio G Blagg Brian S J BS

ACS medicinal chemistry letters 20131126 1

Inhibition of Hsp90 C-terminal function is an advantageous therapeutic paradigm for the treatment of cancer. Currently, the majority of Hsp90 C-terminal inhibitors are derived from novobiocin, a natural product traditionally used as an antibiotic. Assisted by molecular docking studies, a scaffold containing a biphenyl moiety in lieu of the coumarin ring system found in novobiocin was identified for development of new Hsp90 C-terminal inhibitors. Initial structure-activity studies led to derivati ...[more]

PMID: 24900777

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