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The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity.

ABSTRACT: The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anti-cancer design efforts targeting HDAC proteins.

SUBMITTER: Choi SE

PROVIDER: S-EPMC3842171 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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The structural requirements of histone deacetylase inhibitors: Suberoylanilide hydroxamic acid analogs modified at the C3 position display isoform selectivity.

Choi Sun Ea SE Weerasinghe Sujith V W SV Pflum Mary Kay H MK

Bioorganic & medicinal chemistry letters 20110812 20

The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was modified to improve its selectivity for a single histone deaetylase (HDAC) isoform. We show that attaching an ethyl group at the C3 position transforms SAHA from nonselective to an HDAC6-selective inhibitor. Theses results indicate that small structural changes in SAHA can significantly influence selectivity, which will lead future anti-cancer design efforts targeting HDAC proteins. ...[more]

PMID: 21889343

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