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Evaluation of class I HDAC isoform selectivity of largazole analogues.

ABSTRACT: Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement for efficient HDAC inhibition and that substitution of the trans-alkene in the linker with an aromatic group results in complete loss of activity. This data will aid the design of class I isoform selective HDAC inhibitors.

SUBMITTER: Kim B

PROVIDER: S-EPMC4135083 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Evaluation of class I HDAC isoform selectivity of largazole analogues.

Kim Bumki B Park Heekwang H Salvador Lilibeth A LA Serrano Patrick E PE Kwan Jason C JC Zeller Sabrina L SL Chen Qi-Yin QY Ryu Soyoung S Liu Yanxia Y Byeon Seongrim S Luesch Hendrik H Hong Jiyong J

Bioorganic & medicinal chemistry letters 20140709 16

Largazole is a potent class I selective histone deacetylase (HDAC) inhibitor. The majority of largazole analogues to date have modified the thiazole-thiazoline and the warhead moiety. In order to elucidate class I-specific structure-activity relationships, a series of analogues with modifications in the valine or the linker region were prepared and evaluated for their class I isoform selectivity. The inhibition profile showed that the C2 position of largazole has an optimal steric requirement fo ...[more]

PMID: 25070421

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