Toceranib phosphate  (Synonyms: SU11654 phosphate; PHA 291639E phosphate)

Toceranib phosphate (SU11654 phosphate) is an orally active receptor tyrosine kinase (RTK) inhibitor, and it potently inhibits PDGFR, VEGFR, and Kit with K_is of 5 and 6 nM for PDGFRβ and Flk-1/KDR, respectively. Toceranib phosphate (SU11654 phosphate) has antitumor and antiangiogenic activity, and used in the treatment of canine mast cell tumors^{[1] [2]}.

Toceranib phosphate (PHA 291639 phosphate) 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 K_is of 5 and 6 nM, respectively^[1].
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 naïve, 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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Administration of Toceranib phosphate (PHA 291639 phosphate) significantly decreases the number and percentage of Treg in the peripheral blood of dogs with cancer. Dogs receiving Toceranib phosphate (PHA 291639 phosphate) 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^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

494.45

C₂₂H₂₈FN₄O₆P

874819-74-6

Solid

Yellow to orange

O=C(NCCN1CCCC1)C2=C(NC(/C=C3C(NC4=C\3C=C(C=C4)F)=O)=C2C)C.O=P(O)(O)O

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. London CA, et al. Phase I dose-escalating study of SU11654, a small molecule receptor tyrosine kinase inhibitor, in dogs with spontaneous malignancies. Clin Cancer Res. 2003 Jul;9(7):2755-68.  [Content Brief]

  [2]. Halsey CH, et al. Development of an in vitro model of acquired resistance to toceranib phosphate (Palladia?) in canine mast cell tumor. BMC Vet Res. 2014 May 6;10:105.  [Content Brief]

  [3]. Mitchell L, et al. Clinical and immunomodulatory effects of toceranib combined with low-dose cyclophosphamide in dogs with cancer. J Vet Intern Med. 2012 Mar-Apr;26(2):355-62.  [Content Brief]

  [4]. London C, Mathie T, Stingle N, et al. Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours. Vet Comp Oncol. 2012;10(3):194-205.  [Content Brief]