Evaluation of class I HDAC isoform selectivity of largazole analogues.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kim, B; Park, H; Salvador, LA; Serrano, PE; Kwan, JC; Zeller, SL; Chen, Q-Y; Ryu, S; Liu, Y; Byeon, S; Luesch, H; Hong, J

Published Date

  • August 2014

Published In

Volume / Issue

  • 24 / 16

Start / End Page

  • 3728 - 3731

PubMed ID

  • 25070421

Pubmed Central ID

  • PMC4135083

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2014.07.006


  • eng