AUTHOR=Du Tingting , Zhang Zhihui , Zhou Jie , Sheng Li , Yao Haiping , Ji Ming , Xu Bailing , Chen Xiaoguang 

TITLE=A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.865085

DOI=10.3389/fphar.2022.865085

ISSN=1663-9812

ABSTRACT=<p>PARP inhibitors have clinically demonstrated good antitumor activity in patients with BRCA mutations. Here, we described YHP-836, a novel PARP inhibitor, YHP-836 demonstrated excellent inhibitory activity for both PARP1 and PARP2 enzymes. It also allosterically regulated PARP1 and PARP2 via DNA trapping. YHP-836 showed cytotoxicity in tumor cell lines with BRCA mutations and induced cell cycle arrest in the G2/M phase. YHP-836 also sensitized tumor cells to chemotherapy agents <italic>in vitro</italic>. Oral administration of YHP-836 elicited remarkable antitumor activity either as a single agent or in combination with chemotherapy agents <italic>in vivo</italic>. These results indicated that YHP-836 is a well-defined PARP inhibitor.</p>