SZM-1209

SZM-1209 is an inhibitor of receptor-interacting serine/threonine kinase 1 (RIPK1). It selectively binds to RIPK1 over RIPK3 (Kds = 85 and >10,000 nM, respectively) and inhibits necrosome formation and phosphorylation of RIPK1 induced by TNF-alpha, SM-164 (Cay-28632), and Z-VAD-FMK in HT-29 cells (EC50 = 22.4 nM). SMZ-1209 (10 and 20 mg/kg) decreases reductions in body temperature and improves survival in a mouse model of systemic inflammatory response syndrome (SIRS) induced by TNF-alpha and Z-VAD-FMK. It also reduces lung RIPK1 phosphorylation, IL-6 and TNF-alpha levels, and total protein content, as well as decreases the number of hemorrhagic sites and congestion edema, in a mouse model of acute lung injury (ALI) induced by short-term intratracheal exposure to 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK, Cay-16414).Formal Name: N-[5-[[2-[[[4-[(ethylsulfonyl)amino]cyclohexyl]carbonyl]amino]-5-fluoro-6-benzothiazolyl]oxy]-2-fluorophenyl]-3-(trifluoromethyl)-benzeneacetamide. CAS Number: 2919801-86-6. Molecular Formula: C31H29F5N4O5S2. Formula Weight: 696.7. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 15 mg/ml, DMSO: 10 mg/ml. SMILES: FC1=CC2=C(SC(NC(C3CCC(NS(CC)(=O)=O)CC3)=O)=N2)C=C1OC4=CC=C(F)C(NC(CC5=CC=CC(C(F)(F)F)=C5)=O)=C4. InChi Code: InChI=1S/C31H29F5N4O5S2/c1-2-47(43,44)40-20-8-6-18(7-9-20)29(42)39-30-38-25-15-23(33)26(16-27(25)46-30)45-21-10-11-22(32)24(14-21)37-28(41)13-17-4-3-5-19(12-17)31(34,35)36/h3-5,10-12,14-16,18,20,40H,2,6-9,13H2,1H3,(H,37,41)(H,38,39,42). InChi Key: GNCSJDDZYVYRGS-UHFFFAOYSA-N.