@article{APS10805,
author = {Zuo-wei Wang and Feng-ming Zou and Ao-li Wang and Jing Yang and Rui Jin and Bei-lei Wang and Li-juan Shen and Shuang Qi and Juan Liu and Jing Liu and Wen-chao Wang and Qing-song Liu},
title = {Repurposing of the FGFR inhibitor AZD4547 as a potent inhibitor of necroptosis by selectively targeting RIPK1},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {4},
year = {2023},
keywords = {},
abstract = {Necroptosis is a form of regulated necrosis involved in various pathological diseases. The process of necroptosis is controlled by receptor-interacting kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase domain-like protein (MLKL), and pharmacological inhibition of these kinases has been shown to have therapeutic potentials in a variety of diseases. In this study, using drug repurposing strategy combined with high-throughput screening (HTS), we discovered that AZD4547, a previously reported FGFR inhibitor, is able to interfere with necroptosis through direct targeting of RIPK1 kinase. In both human and mouse cell models, AZD4547 blocked RIPK1-dependent necroptosis. In addition, AZD4547 rescued animals from TNF-induced lethal shock and inflammatory responses. Together, our study demonstrates that AZD4547 is a potent and selective inhibitor of RIPK1 with therapeutic potential for the treatment of inflammatory disorders that involve necroptosis.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10805}
}