J Med Chem. 2006 Aug 10;49(16):4809-12.

Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate.

Suzuki T, Kouketsu A, Itoh Y, Hisakawa S, Maeda S, Yoshida M, Nakagawa H, Miyata N.

Source

Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp

Abstract

To find novel histone deacetylase 6 (HDAC6)-selective inhibitors and clarify the structural requirements for HDAC6-selective inhibition, we prepared thiolate analogues designed based on the structure of an HDAC6-selective substrate and evaluated the histone/alpha-tubulin acetylation selectivity by Western blot analysis. Aliphatic compounds 17b-20b selectively caused alpha-tubulin acetylation over histone H4 acetylation. In enzyme assays using HDAC1, HDAC4, and HDAC6, compounds 17a-19a exhibited HDAC6-selective inhibition over HDAC1 and HDAC4.

PMID:: 16884291; [PubMed - indexed for MEDLINE]

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