Ro 5126766

Ro 5126766 is a dual inhibitor of MEK1 (IC50 = 160 nM) and Raf kinases (IC50s = 56, 19, and 8.2 nM for C-RAF, B-RAF, and B-RAFV600E, respectively). It is selective for these kinases over a panel of 254 additional kinases at 10 µM. Ro 5126766 (1 µM) decreases MEK and ERK phosphorylation in a panel of seven cancer cell lines expressing mutant K-RasG13D, K-RasQ61K, K-RasG12D, H-RasG12D, or B-RAFV600E at 1 µM. It inhibits proliferation of SK-MEL-28, SK-MEL-2, MIA PaCa-2, SW480, and HCT116 cancer cells (IC50s = 65, 28, 40, 46, and 277 nM, respectively) but not A549, HCT15, or PC3 cancer cells (IC50s = >1,000 nM for all). Oral administration of Ro 5126766 (25 mg/kg four times per day) reduces tumor growth in an HCT116 mouse xenograft model.Formal Name: N-[3-fluoro-4-[[4-methyl-2-oxo-7-(2-pyrimidinyloxy)-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N'-methyl-sulfamide. CAS Number: 946128-88-7. Synonyms: Avutometinib, CH5126766, VS-6766. Molecular Formula: C21H18FN5O5S. Formula Weight: 471.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: soluble. lambdamax: 278, 316 nm. SMILES: CC(C(C=C1)=C(O2)C=C1OC3=NC=CC=N3)=C(CC4=CC=NC(NS(NC)(=O)=O)=C4F)C2=O. InChi Code: InChI=1S/C21H18FN5O5S/c1-12-15-5-4-14(31-21-25-7-3-8-26-21)11-17(15)32-20(28)16(12)10-13-6-9-24-19(18(13)22)27-33(29,30)23-2/h3-9,11,23H,10H2,1-2H3,(H,24,27). InChi Key: LMMJFBMMJUMSJS-UHFFFAOYSA-N.