Toceranib

Research use only, not for human use.

Toceranib phosphate is an orally active inhibitor of tyrosine kinase (RTK) receptor, and it potently inhibits PDGFR, VEGFR, and Kit(with Kis of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively), has antitumor and antiangiogenic activity.

Toceranib phosphate is an orally active inhibitor of tyrosine kinase (RTK) receptor, and it potently inhibits PDGFR, VEGFR, and Kit(with Kis of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively), has antitumor and antiangiogenic activity.Administration of toceranib significantly decreased the number and percentage of Treg in the peripheral blood of dogs with cancer. Dogs receiving toceranib and CYC demonstrated a significant increase in serum concentrations of IFN-γ, which was inversely correlated with Treg numbers after 6 weeks of combination treatment.

Toceranib (SU11654) is a selective inhibitor of the tyrosine kinase activity of several members of the split kinase RTK family, including PDGFR and Flk-1/KDR, with Kis of 5 and 6 nM, respectively. To explore mechanisms of acquired Toceranib (TOC) resistance in canine MCT, three resistant sublines are generated from the Toceranib-sensitive exon 11 ITD c-kit mutant C2 cell line designated TR1, TR2, and TR3. Growth of the parental C2 cells is inhibited by Toceranib in a dose-dependent manner with an IC50 of <10 nM. In contrast, TR1, TR2, and TR3 sublines are resistant to inhibition by Toceranib (IC50>?1,000 nM). Sensitivity to three other KIT RTK inhibitors is similar to the observed resistance to Toceranib. The parental line as well as all three sublines retains sensitivity to the cytotoxic agents vinblastine (VBL) and CCNU. Following 72 hr culture in the presence of increasing concentrations of Toceranib, treatment na?ve, parental C2 cells detach from the culture flask and become rounded, shrunken, and clumped with increased exposure to Toceranib. In contrast, Toceranib-induced morphologic differences are not identified in the resistant sublines.

Administration of Toceranib significantly decreases the number and percentage of Treg in the peripheral blood of dogs with cancer. Dogs receiving Toceranib and cyclophosphamide (CYC) demonstrate a significant increase in serum concentrations of IFN-γ, which is inversely correlated with Treg numbers after 6 weeks of combination treatment.

SU11654,PHA 291639E

Angiogenesis

PDGFR

PDGFR|VEGFR|Kit

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356068-94-5

396.46

C22H25FN4O2

>98% (HPLC)

DMSO:2.4 mg/mL (6.05 mM; Need ultrasonic)

Cc1[nH]c(\C=C2/C(=O)Nc3ccc(F)cc23)c(C)c1C(=O)NCCN1CCCC1

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(-20℃)

With Ice Pack

≥ 2 years