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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Review Article

Synthetic PARP-1 Inhibitors Reported During the Last Decade

Author(s): Maneesh Guleria, Pradeep Kumar* and Suresh Thareja

Volume 20, Issue 7, 2023

Published on: 27 August, 2022

Page: [793 - 807] Pages: 15

DOI: 10.2174/1570180819666220615090709

Price: $65

Abstract

Background: Cancer is the world's second-largest cause of death, and is responsible for an estimated 9.6 million mortality cases in 2018. Poly-ADP-ribose polymerases (PARPs) are enzymes and a family of proteins involved in many cellular processes, including DNA repair, gene regulation, chromatin remodeling, and apoptosis. The first characterized and best-known member of the PARP family is poly(ADP-ribose) polymerase 1 (PARP-1). PARP-1 is a major protein for DNA single-strand breaks in the BER pathway (base excision repair) (SSBs).

Objective: The objective of this article was to compile synthetic PARP-1 inhibitors reported in the last decade.

Methods: In the present manuscript, bibliographic investigation was carried out by scrutinizing peerreviewed articles from online/offline databases. The inclusion criteria consisted of the most relevant studies indicating the relationship between PARP-1 and cancer in textbooks/edited books and peer-reviewed papers from scientific databases, like SCOPUS, PUBMED, NISCAIR, and Google Scholar since 2010 to 2020. Only the studies published in English language were searched/considered. The exclusion criteria consisted of the studies on other PARP isoforms than PARP-1. The studies thus obtained were classified according to the heterocyclic moieties, year of publication, etc. The data compiled in this article is a systematic review of the reported studies.

Results: The literature reports indicated that a number of PARP-1 inhibitors reported have IC50 value in nanomolar concentration.

Conclusion: PARP-1 is an essential target for anti-cancer drug discovery. Further research on more effective and safe PARP-1 inhibitors needs to be carried out, and we may discover some novel PARP-1 inhibitors in the near future.

Keywords: Cancer, PARP, PARP-1, FDA-approved inhibitors, PARP-1 inhibitors, SSBs.

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