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ID: ALA3585313
Journal: J Med Chem
Title: Fragment-Based Discovery of a Small Molecule Inhibitor of Bruton's Tyrosine Kinase.
Authors: Smith CR, Dougan DR, Komandla M, Kanouni T, Knight B, Lawson JD, Sabat M, Taylor ER, Vu P, Wyrick C.
Abstract: 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.
CiteXplore: 26087137