DNL343

DNL343 is an activator of eukaryotic translation initiation factor 2B (eIF2B, IC50 = 9.8 nM in a reporter assay) and a derivative of 2BAct (Cay-37788). It inhibits sodium arsenite-induced formation of stress granules positive for TAR DNA-binding protein 43 (TDP-43) in an in vitro model of amyotrophic lateral sclerosis (ALS) using H4 cells (IC50 = 12.46 nM). DNL343 (50 mg/kg) decreases the expression of integrated stress response (ISR) genes in Eif2b5R191H mutant mice in a model of neurodegeneration.Formal Name: 2-(4-chlorophenoxy)-N-[3-[5-[cis-3-(trifluoromethoxy)cyclobutyl]-1,3,4-oxadiazol-2-yl]bicyclo[1.1.1]pent-1-yl]-acetamide. CAS Number: 2278265-85-1. Molecular Formula: C20H19ClF3N3O4. Formula Weight: 457.8. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml, DMSO: Sparingly soluble: 1-10 mg/ml, Ethanol: Sparingly soluble: 1-10 mg/ml. SMILES: O=C(NC1(C2)CC2(C1)C3=NN=C([C@H]4C[C@@H](OC(F)(F)F)C4)O3)COC5=CC=C(Cl)C=C5. InChi Code: InChI=1S/C20H19ClF3N3O4/c21-12-1-3-13(4-2-12)29-7-15(28)25-19-8-18(9-19,10-19)17-27-26-16(30-17)11-5-14(6-11)31-20(22,23)24/h1-4,11,14H,5-10H2,(H,25,28)/t11-,14+,18?,19?. InChi Key: IKPNRMYDOSNVAU-QEJBIBHGSA-N.