Histone deacetylase 2 selective inhibitors: A versatile therapeutic strategy as next generation drug target in cancer therapy

Shetty, Manasa Gangadhar and Pai, Padmini and Deaver, Renita Esther and Kapaettu, Satyamoorthy and Kampa, Babitha Sundara (2021) Histone deacetylase 2 selective inhibitors: A versatile therapeutic strategy as next generation drug target in cancer therapy. Pharmacological Research, 170. pp. 1-13. ISSN 1043-6618

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Abstract

Acetylation and deacetylation of histone and several non-histone proteins are the two important processes amongst the different modes of epigenetic modulation that are involved in regulating cancer initiation and development. Abnormal expression of histone deacetylases (HDACs) is often reported in various types of cancers. Few pan HDAC inhibitors have been approved for use as therapeutic interventions for cancer treatment including vorinostat, belinostat and panobinostat. However, not all the HDAC isoforms are abnormally expressed in certain cancers, such as in the case of, ovarian cancer where overexpression of HDAC1-3, lung cancer where overexpression of HDAC 1 and 3 and gastric cancer where overexpression of HDAC2 is seen. Therefore, pan-inhibition of HDAC is not an efficient way to combat cancer via HDAC inhibition. Hence, isoform-selective HDAC inhibition can be one of the best therapeutic strategies in the treatment of cancer. In this context since aberrant expression of HDAC2 largely contributes to cancer progression by silencing pro-apoptotic protein expressions such as NOXA and APAF1 (caspase 9-activating proteins) and inactivation of tumor suppressor p53, HDAC2 specific inhibitors may help to develop not only the direct targets but also indirect targets that are crucial for tumor development. However, to develop a HDAC2 specific and potent inhibitor, extensive knowledge of its structure and specific functions is essential. The present review updates details on the structural features, physiological functions, and roles of HDAC2 in different types of cancer, emphasizing the challenges and status of the development of HDAC2 selective inhibitors against various types of cancer

Item Type: Article
Uncontrolled Keywords: Class I HDACs Selective inhibitor Apoptosis Transcription factor HDAC2 Chemical compounds studied in this article: Vorinostat (PubChem CID: 5311) Panobinostat (PubChem CID: 6918837) Belinostat (PubChem CID: 6918638) Trichostatin A (PubChem CID: 444732) Romidepsin (PubChem CID: 535206) Valproic acid (PubChem CID: 3121) N-(2-aminophenyl) benzamide (PubChem CID: 759408) BRD4884 (PubChem CID: 71465631) 4-(acetylamino)-N-[2-amino-5-(thiophen-2-yl)
Subjects: Life Sciences > MLSC Manipal
Depositing User: KMC Library
Date Deposited: 01 Feb 2022 10:49
Last Modified: 01 Feb 2022 10:49
URI: http://eprints.manipal.edu/id/eprint/158257

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