Lianchao Liu, Lijie Zhao, Lujun Yang, Minxue Chai, Zhengyong Liu, Nan Ma, Yongxing Wang, Qinxue Wu, Jing Guo, Fengtao Zhou, Weixue Huang, Xiaomei Ren, Jian Wang, Ming Ding, Zhen Wang, Ke Ding
Discoidin domain receptor 1 (DDR1) is a potential target for cancer drug discovery. Although several DDR1 kinase inhibitors have been developed, recent studies have revealed the critical roles of the noncatalytic functions of DDR1 in tumor progression, metastasis, and immune exclusion. Degradation of DDR1 presents an opportunity to block its noncatalytic functions. Here, we report the discovery of the DDR1 degrader LLC355 by employing autophagosome-tethering compound technology. Compound LLC355 efficiently degraded DDR1 protein with a DC50 value of 150...
May 10, 2024: Journal of Medicinal Chemistry