AS-703026

The mitogen-activated protein kinases, MEK1 and 2, are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the Ras-Raf-MEK-ERK pathway and are often upregulated in a variety of cancer cell types. AS-703026 is an orally bioavailable small molecule that selectively binds to and inhibits MEK1/2, preventing the activation of downstream effector proteins and transcription factors. It potently inhibits growth and survival of human INA-6 multiple myeloma cells and cytokine-induced osteoclast differentiation with IC50 values of 10 and 18.2 nM, respectively. In mice bearing H929 MM xenograft tumors, 30 mg/kg AS-703026 reduced tumor growth significantly, which correlated with downregulated ERK1/2 activity, induced PARP cleavage, and decreased microvessels in vivo. At 10 µM, AS-703026 supressed proliferation and transformation of K-Ras mutated colorectal cancer cells resistant to EGFR antibody therapy.Formal Name: N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-4-pyridinecarboxamide. CAS Number: 1236699-92-5. Synonyms: MSC1936369B, Pimasertib. Molecular Formula: C15H15FIN3O3. Formula Weight: 431.2. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml, Ethanol: 1 mg/ml. lambdamax: 204, 284, 353 nm. SMILES: O=C(NC[C@H](O)CO)C1=CC=NC=C1NC2=C(F)C=C(I)C=C2. InChi Code: InChI=1S/C15H15FIN3O3/c16-12-5-9(17)1-2-13(12)20-14-7-18-4-3-11(14)15(23)19-6-10(22)8-21/h1-5,7,10,20-22H,6,8H2,(H,19,23)/t10-/m0/s1. InChi Key: VIUAUNHCRHHYNE-JTQLQIEISA-N.