The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of inflammatory bowel disease-Reference-Cited by-同舟云学术

The potent and selective RIPK2 inhibitor BI 706039 improves intestinal inflammation in the TRUC mouse model of inflammatory bowel disease

Published:2021-11-01 Issue:5 Volume:321 Page:G500-G512
ISSN:0193-1857
Container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology
language:en
Short-container-title:American Journal of Physiology-Gastrointestinal and Liver Physiology

Author:

Ermann Joerg¹²,Matmusaev Mederbek¹,Haley Emma K.¹,Braun Clemens³,Jost Felix³,Mayer-Wrangowski Svenja³,Hsiao Peng³,Ting Naitee⁴,Li Li⁴,Terenzio Donna⁵,Chime Jane⁵,Lukas Susan⁵,Patnaude Lori⁵,Panzenbeck Mark⁵,Csordas David⁵,Zheng Jie⁵,Mierz Diane⁵,Simpson Tom⁵,King F. James⁵,Klimowicz Alex P.⁵,Mbow M. Lamine⁵,Fine Jay S.⁵,Miller Craig A.⁵,Fogal Steve E.⁵,Byrne Fergus R.⁵^ORCID

Affiliation:

1. Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Boston, Massachusetts

2. Harvard Medical School, Boston, Massachusetts

3. Department of Drug Discovery Sciences, Boehringer-Ingelheim Pharmaceuticals Incorporated, Biberach, Germany

4. Department of Global Computational Biology and Data Sciences, Boehringer-Ingelheim Pharmaceuticals Incorporated, Ridgefield, Connecticut

5. Department of Immunology and Respiratory Diseases Research, Boehringer-Ingelheim Pharmaceuticals Incorporated, Ridgefield, Connecticut

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.

Funder

Boehringer-Ingelheim

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpgi.00163.2021

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