The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of inflammatory bowel disease
Joerg Ermann, Mederbek Matmusaev, Emma K. Haley, Clemens Braun, Felix Jost, Svenja Mayer‐Wrangowski, Peng Hsiao, Naitee Ting, Li Li, Donna Terenzio, Jane Chime, Susan Lukas, Lori Patnaude, Mark Panzenbeck, David Csordas, Jie Zheng, Diane V. Mierz, T. R. Simpson, Frederick J. King, Alex P. Klimowicz, M. Lamine Mbow, Jay S. Fine, Craig Miller, Steve Fogal, Fergus R. Byrne
Abstract
The RIPK2 kinase at the apex of microbiome immunosensing is an attractive target for pharmacological intervention. A low oral dose of a RIPK2 inhibitor leads to significantly improved intestinal inflammation in the murine TRUC model of colitis. A selective and potent inhibitor of the RIPK2 kinase may represent a new class of therapeutics that target microbiome-driven signaling for the treatment of IBD.