Discovery, evolution, and clinical use of poly(adenosine-diphosphate-ribose)polymerase-1,2 (PARP-1,2) inhibitors

Poly(ADP-ribose)polymerase (PARP) is an important enzyme in cancer drug development because of its wide variety of therapeutic activities. A lot of studies and researches were performed since the 1980s, and more researches are still going on for drug designs and clinical functions.;In this review, a basic knowledge, a history of PARP, and the background information of PARP-1 as an enzyme were discussed in the beginning. In order to check its therapeutic use, breast cancer mutant tumors of BRCA-1 and -2 were explained and their interactions with PARP-1. Also, a detailed mechanism of PARP-1 in damaged DNA repairing system was introduced along with its function as an enzyme. For better understanding of therapeutic purposes of PARP-1, more detailed mechanisms and examples were brought up during "Oncology" and "Ischemia" chapters. At last, different kinds of PARP-1 inhibitors from various core structures were introduced. Those different structures were organized in their scaffolds according to their nicotinamide binding sites. In that chapter, detailed structures and names of each inhibitor were explained by the information of where the structures were derived from. Furthermore, the different structural elements affecting the inherent potency of PARP-1 pharmacophore were explained with couple research examples. At last, one of the new classes of PARP-1 inhibitor was introduced with its synthesis and biological activity.;Although there are several challenges for PARP associated with development of cancer drug development, discoveries and developments of new PARP inhibitor classes play very important roles in the field of medical chemistry.