M-475271 (AZM475271) is an investigational drug targeting cancer invasion and metastasis. It is an aminoquinoline class inhibitor with high affinity and specificity for the nonreceptor tyrosine kinase (Src). In vitro AZM475271 demonstrated strong dose-dependent inhibition of Src tyrosine kinase activity in the L3.6pl human pancreatic carcinoma cell line. The IC50 concentration of AZM475271 to inhibit the phosphorylation of c-Src, lck, and c-yes was 0.01, 0.03, and 0.08 uM, respectively, in comparison with an IC50 of 0.7 uM AZM475271 to inhibit KDR. AZM475271 reduced tumor size, vascularity and metastasis, and increased apoptosis in human pancreatic cells grown orthotopically in nude mice. It also exhibited antiangiogenic activity in vitro and in vivo, and sensitized tumor cells to the cytotoxic effects of gemcitabine. The effect of daily oral treatment with M475271 on subcutaneous tumors and lung metastasis caused by human lung adenocarcinoma cells in NK-cell depleted SCID mice demonstrated inhibition of the growth of subcutaneous tumors via inhibition of tumor cells proliferation, VEGF production and/or vascularization in the mice in a dose-dependent manner. In the metastasis model with A549 cells, the lung weight in the M475271 (50 mg/kg)-treated group was less than that of the control group, despite no difference in the number of metastatic nodules. These findings suggest that M475271 may be efficacious in treating pancreatic adenocarcinomas and might be helpful for controlling the progression of human lung adenocarcinomas.