Zhaobing Xu, Yingchun Liu, Baohui Song, Bingjie Ren, Xiongbin Xu, Ruibin Lin, Xiaoyu Zhu, Chen Chen, Shuqun Yang, Yusong Zhu, Wen Jiang, Wei Li, Yuanfeng Xia, Lihong Hu, Shuhui Chen, Chi-Chung Chan, Jian Li, Xiquan Zhang, Ling Yang, Xin Tian, Charles Z Ding
Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. This is attributable to preferential inhibition of CDK4 over CDK6. In our search for a biased CDK4 inhibitor, we discovered a series of pyrimidine-indazole inhibitors. SAR studies led us to TQB3616 as a preferential CDK4 inhibitor. TQB3616 exhibited improvements in both enzymatic and cellular proliferation inhibitory potency when tested side-by-side with the FDA approved palbociclib and abemaciclib...
April 24, 2024: Bioorganic & Medicinal Chemistry Letters