Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. In addition, RTKs are not only critical regulators of normal cellular processes, but also play a key role in the development and progression of many types of cancer. RTKs, including receptor tyrosine kinase proteins that contain a transmembrane domain, and non-receptor tyrosine kinases that do not have a transmembrane domain. Furthermore, the EGFR, FGFR, VEGFR, RET receptor, Eph receptor, and discoid domain receptor (DDR) families are all members of the receptor tyrosine kinase family. Because RTKs coordinate a wide variety of cellular functions, they must be regulated to prevent severe abnormalities in cellular functioning such as cancer.

Toceranib (also known as SU11654 or PHA 291639E) is a potent and orally active receptor tyrosine kinase (RTK) inhibitor. Meanwhile, this compound potently inhibits EGFR, PDGFR, VEGFR, Kit, and Flt-3. Toceranib has antitumor and antiangiogenic activities. Importantly, Toceranib has the potential for the research of recurrent, non-resectable grades 2 and 3 canine mast cell tumors. For example, in canine C2 mastocytoma cell lines, Toceranib inhibits KIT phosphorylation and cell proliferation in a dose-dependent manner. Toceranib significantly decreases the number and percentage of regulatory T cells (Treg) in the peripheral blood of dogs with cancer. Moreover, Toceranib shows increases in serum concentrations of IFN-γ in dogs. This compound also appears to have biological activity against other tumors in dogs such as mammary carcinoma, soft tissue sarcoma, and anal gland adenocarcinoma.

To sum up, Toceranib is a potent and orally active receptor tyrosine kinase (RTK) inhibitor, with antitumor and antiangiogenic activities.

References:

[1] Charles H C Halsey, et al. BMC Vet Res. 2014 May 6;10:105.

[2] L Mitchell, et al. J Vet Intern Med. Mar-Apr 2012;26(2):355-62.