SCIO 469

SCIO 469 is a p38 MAPK inhibitor (IC50 = 9 nM for p38alpha). It is 10-fold selective for p38alpha over p38beta MAPK and 2,000-fold selective over a panel of 20 additional kinases. SCIO 469 inhibits secretion of IL-6 from multiple myeloma patient-derived bone marrow stromal cells (BMSCs) in a concentration-dependent manner. It increases growth inhibition, DNA fragmentation, and caspase-8 and PARP cleavage induced by the proteasome inhibitor PS-341 (bortezomib, Cay-10008822) in MM.1S cells when used at concentrations of 100 and 200 nM. SCIO 469 (150 and 450 mg/kg) reduces microvessel density and tumor load and increases survival in a 5T33MM murine myeloma model.Formal Name: 6-chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-alpha-oxo-1H-indole-3-acetamide. CAS Number: 309913-83-5. Synonyms: Talmapimod. Molecular Formula: C27H30ClFN4O3. Formula Weight: 513.0. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: soluble. lambdamax: 256, 313 nm. SMILES: FC1=CC=C(CN2C[C@@H](C)N(C(C3=CC(C(C(C(N(C)C)=O)=O)=CN4C)=C4C=C3Cl)=O)C[C@@H]2C)C=C1. InChi Code: InChI=1S/C27H30ClFN4O3/c1-16-13-33(17(2)12-32(16)14-18-6-8-19(29)9-7-18)26(35)21-10-20-22(25(34)27(36)30(3)4)15-31(5)24(20)11-23(21)28/h6-11,15-17H,12-14H2,1-5H3/t16-,17+/m0/s1. InChi Key: ZMELOYOKMZBMRB-DLBZAZTESA-N.