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Potential Application of 5-Aryl-Substituted 2-Aminobenzamide

Potential Application of 5-Aryl-Substituted 2-Aminobenzamide


Potential Application of 5-Aryl-Substituted 2-Aminobenzamide Type of HDAC1/2- Selective Inhibitors to Pharmaceuticals

Author(s): , 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 , 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 . Department of Neurology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan

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Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 40 , 2017

DOI : 10.2174/1381612822666161208143417

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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.

Keywords: HDAC1/2-selective inhibitor, isoform-selective HDAC inhibitor, anti-cancer activity, anti-apoptotic activity, neuroprotective activity, mTOR, p70S6K, XIAP.

Current Pharmaceutical Design

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, 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, Department of Neurology, Graduate School of Medicine, Osaka University, Yamadaoka 2-2, Suita, Osaka 565-0871

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.

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