Biochemicals & reagents
1) Degterev et al. (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury Nat.Chem.Biol. 1 112 2) Teng et al. (2005) Structure-activity relationship of novel necroptosis inhibitors Bioorg.Med.Chem.Lett. 15 5039 3) Degterev et al. (2012) Activity and specificity of necrostatin-1, small-molecule inhibitor of RIP1 kinase Cell Death Differ. 20 366 4) Takahashi et al. (2012) Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models Cell Death Dis. 3 e437 5) Degterev et al. (2013) Addendum: Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury Nat.Chem.Biol. 9 192
Necrostatin-1 analogue with superior potency (IC50 = 206nM vs 494nM), selectivity and metabolic stability in blocking RIP1 (1,2). 7-Cl-O-Nec-1 shows no off-target inhibition of indolamine-2,3-deoxygenase (IDO) in contrast to Necrostatin-1 (Nec-1) (3,4). This compound has showed higher activity in inhibiting necroptosis in Jurkat cells than Necrostatin-1 (EC50 = 210 nM vs. EC50 = 490 nM), no non-specific cytotoxicity at high concentrations (100 µM) and reasonable pharmacokinetic characteristics when used in mice (2) and it is recommended for cellular and in vivo use over Necrostatin-1 (5).