Cayman Chemical ExprSIon ProfIlng of ClInI 96
A RIPK1 inhibitor (IC50s 16 and 2500 nM for the human and mouse enzymes respectively) 10000-fold selective for RIPK1 over a panel of 339 kinases at 10 UM inhibits necrotic cell death induced by a combination of TNF-a and the caspase inhibitor QVD-OPh in U937 human monocytic and L929 murine fibrosarcoma cells (IC50s 6 3 and 1300 nM respectively) decreases IL-1B and IL-6 levels in intestinal mucosa tissue isolated from patients with ulcerative colitis at 3-300 nM increases survival in a mouse model of TNF-a-induced lethal shock at 3 10 and 50 mg/kg