AMG 18 (hydrochloride)

AMG 18 is an inhibitor of inositol-requiring enzyme 1alpha (IRE1alpha, IC50 = 0.013 µM). It is selective for IRE1alpha over JNK3 (IC50 = 2.5 µM) and a panel of 100 kinases at 1 µM. AMG 18 inhibits the splicing of X-box binding protein 1 (XBP1) induced by thapsigargin (Cay10522) in a reporter assay using HT-1080 cells. It sensitizes 9591PPT and 53631PPT mouse pancreatic ductal adenocarcinoma (PDAC) cells to radiation when used at concentrations of 2.5 or 5 µM. AMG 18 (10 µM) reverses increases in fibronectin levels in primary human small airway epithelial cells infected with respiratory syncytial virus (RSV). In vivo, AMG 18 (50 mg/kg) decreases blood glucose levels, liver triglyceride and cholesterol levels, and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine- and choline-deficient (MCD) diet. SMILES CC(C=C1)=C(OC2=C(C3=NC(N[C@@H]4CNCCC4)=NC=C3)C=CC=N2)C5=C1C(NS(C6=C(Cl)C=CC=C6)(=O)=O)=CC=C5.Cl InChi Code InChI=1S/C31H29ClN6O3S.ClH/c1-20-13-14-22-23(8-4-11-27(22)38-42(39,40)28-12-3-2-10-25(28)32)29(20)41-30-24(9-6-17-34-30)26-15-18-35-31(37-26)36-21-7-5-16-33-19-21,/h2-4,6,8-15,17-18,21,33,38H,5,7,16,19H2,1H3,(H,35,36,37),1H/t21-,/m0./s1 InChi Key CNWIPRHGMZTPSB-BOXHHOBZSA-N