SGI-7079

SGI-7079 can be in a dose-dependent manner inhibits tumor growth. And at the maximum dose, 67% tumor can be inhibited growth. Mesenchymal cells showed a trend towards a greater sensitivity to the Axl inhibitor SGI-7079, while the combination of SGI-7079 with erlotinib reversed erlotinib resistance in mesenchymal lines expressing Axl and in a xenograft model of mesenchymal NSCLC.

SGI-7079 exhibits a Ki = 5.7 nM for AXL ,and in HEK293T cells (EC50 = 100 nM) inhibits Gas6 ligand-induced tyrosine phosphorylation of human AXL expressed . Similar to AXL, SGI-7079 inhibits TAM family members such as MER and Tyro3, and shows effective inhibition of Syk, Flt1, Flt3, Jak2, TrkA, TrkB, PDGFRβ and Ret kinases. Mesenchymal cells, which have the increase of the receptor tyrosine kinase Axl, show a trend that has greater sensitivity to the Axl inhibitor SGI-7079.

Ethanol:<1 mg/mL,DMSO:84 mg/mL (184.4 mM),H2O:<1 mg/mL

SGI-7079 show inhibition of Axl activation in HEK-293 cells, which were transiently transfected by electroporation with 1 mg FLAG-tagged plasmid containing the human Axl gene and incubated in standard media + 10% FBS for 24 hours.Cells are treated with SGI-7079( concentrations : 0.03, 0.1, 0.3, 1, 3 μmol/L) for 10 minutes. Five minutes before lysis, the cells are stimulated by WI38 conditioned media containing Gas6.

Animal Models: Mouse(NCr-nu/nu female mice) xenograft model of NSCLC using the mesenchymal NSCLC cell line A549Formulation: 0.1N citrate bufferDosages: 10, 25, 50 mg/kgAdministration: p.o.