Ocadusertib (LY3871801, R552) is a potent and selective, allosteric inhibitor of RIPK1 with IC50 of 12-38 nM.
Ocadusertib inhibits necroptotic responses in multiple in vitro immortalized and primary cell-based assays with a potency of 0.4 to 3 nM.
Ocadusertib inhibits TNF/zVAD-induced cell death with a potency of 7 to 9 nM in human whole blood assays.
Ocadusertib shows no significant inhibition in a panel of 105 kinases at 10 uM.
Ocadusertib prevents RIPK1-dependent hypothermia in response to a TNF challenge; inhibits necroptosis-induced skin inflammation in an acute model; and is efficacious in a chronic proliferative dermatitis (Sharpincpdm) model.
