Rational Design and Optimization of Highly Selective CSF1R Inhibitors for the Treatment of Acute Liver Injury
Xue Yuan·Qihai Gong·Yurong Zou·Yuhan Wei·Qianhuan Liu·Guoli Zheng·茹 苗·Yuandong Zhang·Baojian Xiong·Jianmei Gao·Yong Chen·Kongjun Liu
Colony-stimulating factor 1 receptor (CSF1R) is a key regulator of macrophage-driven liver inflammation. Here, we report a series of CSF1R inhibitors discovered through a structure-guided optimization strategy for the acute-phase treatment of acetaminophen-induced liver injury. For instance, compound <b>C52</b> exhibited potent CSF1R inhibition, a kinome-wide selective profile, and low cellular cytotoxicity. <b>C52</b> rapidly suppressed M-CSF-induced phosphorylation events and downstream signal