Antitumor activity of a novel PARP1/2 inhibitor YHP-743

VernacularTitle:新型PARP1/2抑制剂YHP-743的抗肿瘤作用
Author: Ming JI ¹ ; Hai-ping YAO ¹ ; Jie ZHOU ¹ ; Jing JIN ¹ ; Li-yuan WANG ¹ ; Fang-fang LAI ¹ ; Ni-na XUE ¹ ; Bai-ling XU ¹ ; Xiao-guang CHEN ¹
Author Information

1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines/Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China
Publication Type:ORIGINAL ARTICLES
Keywords: poly (ADP-ribose) polymerase-1; poly (ADP-ribose) polymerase-2; DNA repair; antitumor activity; inhibitor
From: Acta Pharmaceutica Sinica 2018;53(6):938-943
CountryChina
Language:Chinese
Abstract: Poly(ADP-ribose) polymerase (PARP)-1 and PARP2 function as ADP-ribosylases involved in DNA repair. PARP1/2 is highly expressed in cancers and emerged as an attractive target for antitumor drug. In this study, we investigated the antitumor activity of a novel PARP1/2 inhibitor YHP-743 in vitro and in vivo. The results showed that YHP-743 had potent enzymatic inhibitory activity against PARP1 and PARP2 to down-regulate the PAR level. YHP-743 not only inhibited breast cancer cells with genes deficiency of homologous recombination repair, but also potentiated chemotherapy agent's cytotoxicity, such as temozolomide, topotecan, cisplatin and doxorubicin. YHP-743 elicited good antitumor activity in combination with temo-zolomide in vivo.