GSK2983559 is a receptor-interacting protein kinase 2 (RIPK2) inhibitor.1 It inhibits RIPK2 by 65% in a kinase assay when used at a concentration of 10 ?M. GSK2983559 (10 ?M) also inhibits VEGFR3 by greater than 90%, as well as 14 additional kinases by 60 to 89% in a panel of 344 kinases. In vivo, GSK2983559 (7.5 and 145 mg/kg twice per day) reduces colonic damage in a mouse model of TNBS-induced colitis. GSK2983559 is also a prodrug that is cleaved to an active metabolite in the gastrointestinal tract that inhibits RIPK2 more potently than GSK2983559.
1.Haile, P.A., Casillas, L.N., Votta, B.J., et al.Discovery of a first-in-class receptor interacting protein 2 (RIP2) kinase specific clinical candidate, 2-((4-(benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl dihydrogen phosphate, for the treatment of inflammatory diseasesJ. Med. Chem.62(14)6482-6494(2019)