Axitinib

KIT

386, 47

BT474 breast cancer cells are implanted subcutaneously into Immune-deficient female mice (Nu/nu, age 8–12 weeks).

Axitinib is currently in Phase III clinical trial in advanced hepatocellular carcinoma.

10, 30 or 100 mg/kg

0.1 nM, 0.1 nM, 0.1 nM, 0.1 nM, 0.1 nM, 0.1 nM

Axitinib exhibits primary inhibition to orthotopically transplanted models such as M24met (melanoma), HCT-116 (colorectal cancer), and SN12C (renal cell carcinoma). [1] Axitinib delays the tumor growth with 11.4 days compared to the controls (p.o. 30 mg/kg) and decreases the Mean Vessels Density (MVD) to 21, compared to 49 in controls, in IGR-N91 ank xenografts. [2] Axitinib significantly inhibits growth and disrupts tumor microvasculature in BT474 breast cancer model at 10-100 mg/kg. [3] Axitinib has shown single-agent activity in variable tumors, including renal cell carcinoma, thyroid cancer, non-small cell lung cancer, and melanoma.

Cellular receptor kinase phosphorylation assay, Porcine aorta endothelial (PAE) cells, which overexpress full-length VEGFR2, PDGFRbeta, Kit, and NIH-3T3, which overexpress murine VEGFR2 (Flk-1) or PDGFRalpha, are generated. The 96-well plates are coated with 100 uL/well of 2.5 ug/mL anti-VEGFR2 antibody, 0.75 ug/mL anti-PDGFRbeta antibody, 0.25 ug/mL anti-PDGFRalpha antibody, 0.5 ug/mL anti-KIT antibody, or 1.20 ug/mL anti-Flk-1 antibody to prepare ELISA capture plates. Then phosphorylation of RTK is measured by ELISA.

DMSO 42 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

Axitinib is superior as second-line therapy compared with sorafenib, the current standard of care.