A Review of PARP-1 Inhibitors: Assessing Emerging Prospects and Tailoring Therapeutic Strategies.

Soundarya Ramesh, Shannon D Almeida, Sameerana Hammigi, Govardan Katta Radhakrishna, Golla Sireesha, Theivendren Panneerselvam, Shangavi Vellingiri, Selvaraj Kunjiappan, Damodar Nayak Ammunje, Parasuraman Pavadai

Journal: Drug research 2023;73(9):491-505

PMID: 37890514

Abstract

Eukaryotic organisms contain an enzyme family called poly (ADP-ribose) polymerases (PARPs), which is responsible for the poly (ADP-ribosylation) of DNA-binding proteins. PARPs are members of the cell signaling enzyme class. PARP-1, the most common isoform of the PARP family, is responsible for more than 90% of the tasks carried out by the PARP family as a whole. A superfamily consisting of 18 PARPs has been found. In order to synthesize polymers of ADP-ribose (PAR) and nicotinamide, the DNA damage nick monitor PARP-1 requires NAD+ as a substrate. The capability of PARP-1 activation to boost the transcription of proinflammatory genes, its ability to deplete cellular energy pools, which leads to cell malfunction and necrosis, and its involvement as a component in the process of DNA repair are the three consequences of PARP-1 activation that are of particular significance in the process of developing new drugs. As a result, the pharmacological reduction of PARP-1 may result in an increase in the cytotoxicity toward cancer cells.

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Address: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India.; Department of Pharmacology, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, M S R Nagar, Bengaluru, India.; Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tamil Nadu, India.; Department of Pharmacy Practice, Swamy Vivekananda College of Pharmacy, Elayampalayam, Tamil Nadu, India.; Department of Biotechnology, Kalasalingam Academy of Research and Education, Krishnankoil, Tamil Nadu, India.
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