title: Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate.
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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Nagoya, Aichi 467-8603, Japan. suzuki@phar.nagoya-cu.ac.jp
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akiyasu
authors.initials: A
authors.lastname: Kouketsu
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Shinya
authors.initials: S
authors.lastname: Hisakawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Maeda
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D013438:Sulfhydryl Compounds; D014404:Tubulin