Cl-Necrostatin-1 is an inhibitor of receptor-interacting protein kinase 1 (RIPK1).1 It inhibits RIPK1 activity when used at concentrations of 0.3, 3, and 30 µM. It also inhibits TNF-α-induced necroptosis in Jurkat cells deficient in Fas-associated death domain protein (FADD; EC50 = 180 nM), a modification that prevents caspase activation in response to death-domain receptor signaling.2,3 Cl-Necrostatin-1 (2 µl of a 4 mM solution, i.c.v.) reduces infarct size when administered pre- and post-occlusion, or post-occlusion only, in a mouse model of middle cerebral artery occlusion (MCAO).
1.Degterev, A., Hitomi, J., Germscheid, M., et al.Identification of RIP1 kinase as a specific cellular target of necrostatinsNat. Chem. Biol.4(5)313-321(2008) 2.Teng, X., Degterev, A., Jagtap, P., et al.Structure-activity relationship study of novel necroptosis inhibitorsBioorg. Med. Chem. Lett.15(22)5039-5044(2005) 3.Degterev, A., Huang, Z., Boyce, M., et al.Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injuryNat. Chem. Biol.1(2)112-119(2005)