Toceranib (SU11654) 是一种口服活性受体酪

Toceranib  (Synonyms: 托西尼布; SU11654; PHA 291639E)

Toceranib (SU11654) 是一种口服活性受体酪氨酸激酶 (RTK) 抑制剂，能有效抑制PDGFR，VEGFR，Kit，抑制 PDGFRβ 和 Flk-1/KDR 的 K_i 值分别为 5 nM 和 6 nM。Toceranib 具有抗肿瘤和抗血管生成活性，用于犬肥大细胞肿瘤的研究。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
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生物活性    
Toceranib phosphate (SU11654 phosphate) is an orally active receptor tyrosine kinase (RTK) inhibitor, and it potently inhibits PDGFR, VEGFR, and Kit with Kis 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].

体外研究(In Vitro)    
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[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].

体内研究(In Vivo)    
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[3].

分子量    
396.46

性状    
Solid

Formula    
C22H25FN4O2

CAS 号    
356068-94-5

中文名称    
托西尼布

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
Powder    -20°C    3 years
4°C    2 years
In solvent    -80°C    6 months
-20°C    1 month
溶解性数据    
In Vitro: 
DMSO : 2.5 mg/mL (6.31 mM; Need ultrasonic)

H2O : 1 mg/mL (2.52 mM; ultrasonic and warming and heat to 80°C)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    2.5223 mL    12.6116 mL    25.2232 mL
5 mM    0.5045 mL    2.5223 mL    5.0446 mL
10 mM    ---    ---    ---
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
 

参考文献

[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]