Medicine and Health

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models

F. Ren, A. Aliper, et al.

This groundbreaking research identifies TRAF2-and NCK-interacting kinase (TNIK) as an anti-fibrotic target for idiopathic pulmonary fibrosis (IPF). Utilizing artificial intelligence, the study introduces INS018_055, a small-molecule TNIK inhibitor that demonstrates significant anti-fibrotic and anti-inflammatory effects in vivo. With successful Phase I clinical trials confirming safety and tolerability, this work by esteemed authors paves the way for AI-driven advancements in drug discovery.

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Abstract

Idiopathic pulmonary fibrosis (IPF) is a deadly lung disease lacking effective therapies. This study identifies TRAF2-and NCK-interacting kinase (TNIK) as an anti-fibrotic target using artificial intelligence (AI). An AI-designed small-molecule TNIK inhibitor, INS018_055, shows anti-fibrotic and anti-inflammatory activity in vivo across various organs. Phase I clinical trials (NCT05154240 and CTR20221542) confirmed its safety and tolerability in healthy participants. This work, completed in 18 months, highlights the potential of AI-driven drug discovery.

Publisher

Nature Biotechnology

Published On

Mar 08, 2024

Authors

Feng Ren, Alex Aliper, Jian Chen, Heng Zhao, Sujata Rao, Christoph Kuppe, Ivan V. Ozerov, Man Zhang, Klaus Witte, Chris Kruse, Vladimir Aladinskiy, Yan Ivanenkov, Daniil Polykovskiy, Yanyun Fu, Eugene Babin, Junwen Qiao, Xing Liang, Zhenzhen Mou, Hui Wang, Frank W. Pun, Pedro Torres-Ayuso, Alexander Veviorskiy, Dandan Song, Sang Liu, Bei Zhang, Vladimir Naumov, Xiaoqiang Ding, Andrey Kukharenko, Evgeny Izumchenko, Alex Zhavoronkov

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