Fragment-based discovery of a small molecule inhibitor of Bruton’s Tyrosine Kinase
Journal Article
·
· Journal of Medicinal Chemistry
- Takeda California, San Diego, CA (United States)
The discovery and optimization of a series of 4-aminocinnoline-3-carboxamide inhibitors of Bruton’s tyrosine kinase are reported. A fragment-based screening approach incorporating X-ray co-crystallography was used to identify a cinnoline fragment and characterize its binding mode in the ATP binding site of Btk. Optimization of the fragment hit resulted in the identification of a lead compound which reduced paw swelling in a dose- and exposure-dependent fashion in a rat model of collagen-induced arthritis.
- Research Organization:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1213735
- Journal Information:
- Journal of Medicinal Chemistry, Vol. 58, Issue 14; ISSN 0022-2623
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- ENGLISH
Cited by: 56 works
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