RIPK1 inhibitor 22 (RIPK1-IN-22) is a highly potent, orally available, and brain-penetrating RIP1 kinase (RIPK1) inhibitor with pKi of 9.04.
RIPK1 inhibitor 22 displays excellent specificity for RIP1 kinase over 406 kinases including RIP3 kinase.
RIPK1 inhibitor 22 strongly suppressed necroptotic cell death and phosphorylation of MLKL (pMLKL) in HT-29 cells (nectoptosis; IC50=2.0 nM, pMLKL; IC50 = 1.3 nM) as well as L929 cells (nectoptosis; IC50=15 nM, pMLKL; IC50=2.7 nM).
RIPK1 inhibitor 22 attenuates disease progression in the mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) after oral administration (10 mg/kg, bid).
