SGI-7079

SGI-7079能够依剂量依赖性抑制肿瘤生长，在最大剂量下，可抑制67%的肿瘤生长。间充质细胞对Axl抑制剂SGI-7079显示出更高的敏感性，同时，SGI-7079与erlotinib的联合使用能够逆转表达Axl的间充质细胞系及间充质非小细胞肺癌（NSCLC）异种移植模型中的erlotinib抗药性。

SGI-7079对AXL的Ki值为5.7 nM，并能在HEK293T细胞中（EC50=100 nM）抑制由Gas6配体诱导的人类AXL的酪氨酸磷酸化。与AXL相似，SGI-7079还能抑制TAM家族成员如MER和Tyro3，同时有效抑制Syk、Flt1、Flt3、Jak2、TrkA、TrkB、PDGFRβ和Ret激酶。表达受体酪氨酸激酶Axl增加的间充质细胞对Axl抑制剂SGI-7079表现出更高的敏感性。

Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:84 mg/mL (184.4 mM);H2O:< 1 mg/mL (insoluble or slightly soluble)

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.