Toceranib is An Orally Active Inhibitor of Receptor Tyrosine Kinase (RTK)
Posted On 2022-07-08
Toceranib is an orally active receptor tyrosine kinase (RTK) inhibitor. Besides, Toceranib inhibits PDGFR, VEGFR, and Kit with Kis of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively. What’s more, Toceranib has antitumor and antiangiogenic activity and has the potential to recurrent, non-resectable grades 2 and 3 canines MCTs.
Toceranib is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including PDGFR and Flk-1/KDR. Recently, research shows that Toceranib inhibits the growth of parental C2 cells in a dose-dependent manner with an IC50 of <10 nM. Besides, Toceranib inhibits KIT phosphorylation in a dose-dependent manner. In contrast, TR1, TR2, and TR3 sublines are resistant to inhibition by Toceranib with IC50 of >1,000 nM. Moreover, Toceranib shows morphologic differences for parental C2 cells. In contrast, Toceranib-induced morphologic differences are not identified in the resistant sublines. Additionally, chronic TOC exposure results in c-kit mRNA and KIT protein overexpression in the TOC-resistant sublines.
Toceranib shows antitumor and antiangiogenic activity.
Toceranib (2.5 mg/kg; p.o.; once every other day for 2 weeks) significantly decreases the number and percentage of Treg in the peripheral blood of dogs with cancer. Moreover, Dogs receiving Toceranib and cyclophosphamide (CYC) (oral CYC was added at 15 mg/m(2)daily) demonstrate a significant increase in serum concentrations of IFN-γ, which is inversely correlated with Treg numbers after 6 weeks of combination treatment.
In conclusion, Toceranib is a selective and orally active inhibitor of receptor tyrosine kinase (RTK). Besides, Toceranib shows antitumor and antiangiogenic activity. Moreover, Toceranib has the potential for the research of canine mast cell tumors.
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