AZM475271 is an inhibitor of c-Src kinase (IC50 = 0.01 ?M).1 It inhibits phosphorylation of c-Src kinase, Lck, c-Yes, and VEGFR2 (IC50s = 0.01, 0.03, 0.08, and 0.7 ?M, respectively).2 AZM475271 inhibits proliferation of NIH3T3 fibroblasts, as well as PC3 and DU145 prostate and A549 lung cancer cells (IC50s = 0.5, 32, 16, and 17 ?M, respectively). It reduces tumor cell proliferation and microvessel density and increases apoptosis in an L3.6pl pancreatic cancer mouse xenograft model when administered at a dose of 50 mg/kg per day. AZM475271 inhibits tumor growth and metastasis in the same mouse xenograft model when administered in combination with gemcitabine .
1.Plé, P.A., Green, T.P., Hennequin, L.F., et al.Discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of c-SrcJ. Med. Chem.47(4)871-887(2004) 2.Yezhelyev, M.V., Koehl, G., Guba, M., et al.Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude miceClin. Cancer Res.10(23)8028-8036(2004)