Selective SIRT2 inhibitors as promising anticancer therapeutics: An update from 2016 to 2020

Eslam Roshdy; Muhamad Mustafa; Abd El-Rahman Shaltout; Mohamed O Radwan; Mahmoud A A Ibrahim; Mahmoud E Soliman; Mikako Fujita; Masami Otsuka; Taha F S Ali

doi:10.1016/j.ejmech.2021.113709

Selective SIRT2 inhibitors as promising anticancer therapeutics: An update from 2016 to 2020

Eur J Med Chem. 2021 Nov 15:224:113709. doi: 10.1016/j.ejmech.2021.113709. Epub 2021 Jul 18.

Authors

Eslam Roshdy¹, Muhamad Mustafa², Abd El-Rahman Shaltout³, Mohamed O Radwan⁴, Mahmoud A A Ibrahim⁵, Mahmoud E Soliman⁶, Mikako Fujita⁷, Masami Otsuka⁸, Taha F S Ali⁹

Affiliations

¹ Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
² Medicinal Chemistry Department, Faculty of Pharmacy, Deraya University, Minia, Egypt. Electronic address: muhamad.mustafa@deraya.edu.eg.
³ Clinical Pharmacy Program, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
⁴ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, School of Pharmacy, Kumamoto University, Kumamoto, 862-0973, Japan; Department of Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan; Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt.
⁵ Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt.
⁶ Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban, 4000, South Africa.
⁷ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, School of Pharmacy, Kumamoto University, Kumamoto, 862-0973, Japan.
⁸ Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, School of Pharmacy, Kumamoto University, Kumamoto, 862-0973, Japan; Department of Drug Discovery, Science Farm Ltd., 1-7-30 Kuhonji, Chuo-ku, Kumamoto, 862-0976, Japan.
⁹ Medicinal Chemistry Department, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt; Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, School of Pharmacy, Kumamoto University, Kumamoto, 862-0973, Japan. Electronic address: Taha.ali@mu.edu.eg.

PMID: 34303869
DOI: 10.1016/j.ejmech.2021.113709

Abstract

Sirtuin 2 (SIRT2) is a member of the human sirtuins, which regulates various biological processes and is deemed as a novel biomarker for different cancers. Depending on the tumor type, SIRT2 knockout leads to a controversial role in tumorigenesis, however, pharmacological inhibition of SIRT2 results exclusively in growth inhibition of various cancer cells. In this respect, selective SIRT2 inhibitors hold therapeutic promise in a wide range of tumors. The literature has a batch of successful stories of SIRT2 modulators discovery. This review presents our perspective on the up-to-date selective SIRT2 inhibitors and their antiproliferative activity.

Keywords: Cancer; Epigenetics; Mechanism-based; NAD-dependent; PROTAC; SIRT2; Selectivity pocket; Sirtuins.

Publication types

Review

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Molecular Structure
Neoplasms / drug therapy*
Neoplasms / pathology
Sirtuin 2 / antagonists & inhibitors*
Sirtuin 2 / metabolism

Substances

Antineoplastic Agents
Enzyme Inhibitors
SIRT2 protein, human
Sirtuin 2