Title:Potential Application of 5-Aryl-Substituted 2-Aminobenzamide Type of HDAC1/2- Selective Inhibitors to Pharmaceuticals
Volume: 23
Issue: 40
Author(s): Shinichi Uesato*, Yoshiyuki Hirata and Tsutomu Sasaki
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
Keywords:
HDAC1/2-selective inhibitor, isoform-selective HDAC inhibitor, anti-cancer activity, anti-apoptotic activity, neuroprotective
activity, mTOR, p70S6K, XIAP.
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.
