Dovitinib-d8

Dovitinib-d8 is intended for use as an internal standard for the quantification of dovitinib by GC- or LC-MS. Dovitinib is a receptor tyrosine kinase inhibitor that targets vascular endothelial growth factor-2, basic fibroblast growth factor-1, and platelet-derived growth factor β receptors (IC50s = 65, 11, and 5 nM, respectively).1 By impairing these kinase signals, 1 μM dovitinib has been shown to prevent the growth and motility of pancreatic cancer cell lines (HPAF-II, BxPC-3, MiaPaCa2, and L3.6pl).2 At 0.04 μM, dovitinib can inhibit endothelial cell proliferation and motility.3 These antiangiogenic effects have been proposed to be the mechanism by which dovitinib inhibits hepatocellular carcinoma growth and metastasis.3 Dovitinib has been evaluated in clinical trials for the treatment of advanced solid tumors.4,5

|1. Renhowe, P.A., Pecchi, S., Shafer, C.M., et al. Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: A novel class of receptor tyrosine kinase inhibitors. J. Med. Chem. 52(2), 278-292 (2009).|2. Taeger, J., Moser, C., Hellerbrand, C., et al. Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer. Mol. Cancer Ther. 10(11), 2157-2167 (2011).|3. Chen, Z.Y., Shi, M., Peng, L.X., et al. Dovitinib preferentially targets endothelial cells rather than cancer cells for the inhibition of hepatocellular carcinoma growth and metastasis. J. Transl. Med. 10:245, (2012).|4. Kim, K.B., Chesney, J., Robinson, D., et al. Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. Clin. Cancer Res. 17(23), 7451-7461 (2011).|5. Sarker, D., Molife, R., Evans, T.R.J., et al. A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin. Cancer Res. 14(7), 2075-2081 (2008).