Document Report Card

ID: ALA1146857

Journal: J Med Chem

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

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

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.

CiteXplore: 16884291

DOI: 10.1021/jm060554y