Trametinib (DMSO solvate)

Trametinib is an inhibitor of MEK1 and -2. It inhibits B-RAF- and C-RAF-induced phosphorylation of MEK1 (IC50s = 3. and 1. nM, respectively) and MEK2 (IC50s = 1. and 0. nM, respectively). Trametinib inhibits the growth of two human colorectal cancer cell lines expressing mutant B-RAF (IC50s = 0. and 0. nM) and seven cell lines expressing mutant K-Ras (IC50s = 2.2-174 nM) but does not inhibit the growth of COLO 320DM cells expressing both wild-type B-RAF and wild-type K-Ras (IC50 = >10,000 nM). It reduces tumor growth in HT-29 and COLO 205 mouse xenograft models when used at doses of 0. and 1 mg/kg per day. Trametinib (0. and 0. mg/kg per day) also decreases M. tuberculosis-induced increases in hind paw volume in a rat model of arthritis. Formulations containing trametinib, in combination with dabrafenib, have been used in the treatment of metastatic mutant B-RAFV600E melanoma. Formal Name: N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-acetamide compd. with 1,1'-sulfinylbis[methane]. CAS Number: 1187431-43-1. Synonyms: GSK1120212 JTP-74057. Molecular Formula: C26H23FIN5O4  C2H6OS. Formula Weight: 693.5. Purity: >98%. Formulation (Request formulation change): A solid. Solubility: Acetonitrile: Slightly soluble: 0.1-1 mg/ml. SMILES: O=S(C)C.CN(C(NC1=CC=C(I)C=C1F)=C2C3=O)C(C(C)=C2N(C(N3C4CC4)=O)C5=CC(NC(C)=O)=CC=C5)=O. InChi Code: InChI=1S/C26H23FIN5O4.C2H6OS/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34.1-4(2)3/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34).1-2H3. InChi Key: OQUFJVRYDFIQBW-UHFFFAOYSA-N. Storage: -20°C. Stability: > 4 years.