title: Potential Application of 5-Aryl-Substituted 2-Aminobenzamide Type of HDAC1/2- Selective Inhibitors to Pharmaceuticals.
abstract: Diverse histone deacetylase (HDAC) inhibitors have been developed to date. They control not only histone modification but also gene expression of diverse proteins and thus are expected to provide useful therapeutic effects on various diseases, including cancers, psychiatric and cognitive disorders and neurodegenerative diseases, as well as cardiovascular and diabetic diseases. Some isoform-nonselective HDAC inhibitors have been successfully used for clinical treatments of the haematological malignancies, including advanced forms of cutaneous T-cell lymphoma, refractory peripheral T-cell lymphoma and multiple myeloma. However, the nonselective HDAC inhibitors threaten to cause adverse effects, such as thrombocytopenia, nausea, fatigue and cardiotoxicity, and their influence on the health care of patients is of concern. It is therefore anticipated that the development of isoform-selective HDAC inhibitors may offer more efficacy and less toxicity. Recently, a number of 5- aryl-substituted 2-aminobenzamide series of HDAC1/2-selective inhibitors have been synthesized, and their useful biological activities have been reported. In this review, we introduce the recent development of synthetic and biological studies on 5-aryl-substituted 2-aminobenzamide-type HDAC1/2 inhibitors, together with the latest research findings on biology of broad-spectrum HDAC inhibitors. In addition, we refer to the possibility of their application in clinical therapies.
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan; Kansai University Center for Innovation and Creativity, Suita, Osaka 564-8680, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
authors.affiliation: Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan; Kansai University Center for Innovation and Creativity, Suita, Osaka 564-8680, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Neurology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D062367:ortho-Aminobenzoates; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; C000219:anthranilamide
keywords: HDAC1/2-selective inhibitor; XIAP.; anti-apoptotic activity; anti-cancer activity; isoform-selective HDAC inhibitor; mTOR; neuroprotective
  activity; p70S6K