Zeren Sun, Lanjie Li, Bingxin Zhai, Mengxuan Hu, Lei Huang, Shihui Huang, Liu Ye, Xiangying Kong, Jie Xu, Jie Bai, Jingjie Yan, Qichen Zhou, Zheqi Hu, Yuchen Zhang, Yuhan Jiang, Yan Zhang, Zhou Qiao, Yi Zou, Yungen Xu, Qihua Zhu
The emergence of resistance to PARP1 inhibitors poses a current therapeutic challenge, necessitating the development of novel strategies to overcome this obstacle. The present study describes the design and synthesis of a series of small molecules that target both PARP1 and c-Met. Among them, compound 16 is identified as a highly potent dual inhibitor, exhibiting excellent inhibitory activities against PARP1 (IC50 = 3.3 nM) and c-Met (IC50 = 32.2 nM), as well as demonstrating good antiproliferative effects on HR-proficient cancer cell lines and those resistant to PARP1 inhibitors...
March 13, 2024: Journal of Medicinal Chemistry