SBI-0640756

SBI-0640756 is an inhibitor of eukaryotic translation initiation factor 4 gamma 1 (eIF4G1). It inhibits the association of eIF4G1 with the eIF4F complex in UACC-903 melanoma cell lysates in an m7GTP-agarose pull-down assay when used at a concentration of 0.75 µM. SBI-0640756 also inhibits eIF4G1-dependent and -independent mRNA translation in reporter assays using rabbit reticulocyte lysates (IC50s = 3.83 and 4.59 µM, respectively). It reduces the growth of 1205Lu, WM1346, A375, UACC-903, and WM3629 melanoma cells in a concentration-dependent manner. SBI-0640756 (0.5 mg/kg) decreases tumor incidence by 50% in an N-RasQ61K-expressing, Ink4a-/- murine melanoma model. It also decreases tumor volume in an A375 mouse xenograft model when used in combination with the B-RAFV600E inhibitor PLX4720 (Cay-15142).Formal Name: (E)-6-chloro-3-(3-(5-fluoropyridin-3-yl)acryloyl)-4-phenylquinolin-2(1H)-one. Synonyms: SBI-756. Molecular Formula: C23H14ClFN2O2. Formula Weight: 404.8. Purity: >95%. Formulation: (Request formulation change), A solid. Solubility: Acetonitrile: Soluble, DMSO: Soluble, Methanol: Soluble. SMILES: ClC1=CC2=C(C=C1)NC(C(C(/C=C/C3=CC(F)=CN=C3)=O)=C2C4=CC=CC=C4)=O. InChi Code: InChI=1S/C23H14ClFN2O2/c24-16-7-8-19-18(11-16)21(15-4-2-1-3-5-15)22(23(29)27-19)20(28)9-6-14-10-17(25)13-26-12-14/h1-13H,(H,27,29)/b9-6+. InChi Key: VVWGPQZBDQVQRC-RMKNXTFCSA-N.