PARG inhibitors’ success: a long way to go!

Abstract

Poly(ADP-ribosyl)ation is one of the most pertinent post translational modifications involved in regulation of chromatin structure, cell cycle progression, tissue development and differentiation and other vital biological phenomena. The enzymes that catalyze the synthesis and degradation of poly(ADP) ribose polymers are PARP and PARG, respectively. The role of PARP has been implicated in development of various diseases since a long time and hence it has evolved as an important pharmacological target but a plethora of drawbacks associated with PARP inhibitors compelled the shift of focus towards PARG. Recently PARG has evolved as an alternative target to overcome the hurdles being faced in the treatment of various conditions like multiple organ failure, ischemic organ damage, diabetic nephropathy, neurodegenerative diseases and cancer. The review provides a compendium on PARG, its mode of action, inhibitors, and its therapeutic applications and also discusses the reasons due to which PARG inhibitors have not been able to reach the clinical trials. PARG inhibitors, though far from success, definitely appear as alluring topics for further research as PARG emerges out as an eminent pharmacological target in making which can shape the future of medicines to provide better therapy with reduced side effects and more efficiency.