Axitinib

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.

Axitinib (AG-013736) is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRbeta and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.

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

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.

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Data from [J Biomol Screen , 2011, 16, 141-154], Axitinibpurchased from Selleck, (A) 3D confocal image (20 objective) of individual whole spheroids fixed and stained for vimentin (green) and DAPI (blue). (B) Representative confocal image (10 objective) of individual spheroids fixed, sectioned, and then stained for vimentin (green) and DNA (DAPI, blue). (C) Vimentin protein expression from sections quantitated from multiple replicate spheroid treatments with U0126 and axitinib using ImageJ software.

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