Cabozantinib 是一种口服有效的 VEGFR2 和

Cabozantinib  (Synonyms: 卡博替尼; XL184; BMS-907351)

Cabozantinib 是一种口服有效的 VEGFR2 和 MET 抑制剂，IC₅₀ 分别为 0.035 和 1.3 nM。Cabozantinib 对 KIT、RET、AXL、TIE2 和 FLT3 有较强的抑制作用 (IC₅₀=4.6、5.2、7、14.3 和 11.3 nM)。Cabozantinib 显示出抗血管生成活性。Cabozantinib 可以破坏肿瘤血管，促进肿瘤和内皮细胞凋亡 (apoptosis)。

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
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。从产品的HNMR数据解析到生物活性数据，从客户的询价到产品的售后服务，我们拥有着完善的管理体系，从而保证我们的服务更加高效、准确。努力为中国的医药行业发展注入新的活力，我们将成为您研发工作值得信赖的伙伴。

生物活性    
Cabozantinib is a potent and orally active inhibitor of VEGFR2 and MET, with IC50 values of 0.035, and 1.3 nM, respectively. Cabozantinib displays strong inhibition of KIT, RET, AXL, TIE2, and FLT3 (IC50=4.6, 5.2, 7, 14.3, and 11.3 nM, respectively). Cabozantinib shows antiangiogenic activity. Cabozantinib disrupts tumor vasculature and promotes tumor and endothelial cell apoptosis

体外研究
(In Vitro)    
Cabozantinib inhibits phosphorylation of MET and VEGFR2, as well as KIT, FLT3, and AXL with IC50 values of 7.8, 1.9, 5.0, 7.5, and 42 μM, respectively[1].
Cabozantinib (4.6 nM) inhibits tubule formation with no evidence of cytotoxicity, with IC50 values of 6.7, 5.1, 4.1, 7.7, and 4.7 nM in HMVEC, MDA-MB-231, A431, HT1080, and B16F10 cells, respectively[1].
Cabozantinib (0-370 nM, 24 h) inhibits cellular migration and invasion[1].
Cabozantinib (48 h) inhibits tumor cell proliferation in a variety of tumor types[1].

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

Cell Proliferation Assay

Cell Line:    SNU-5, Hs746T, SNU-1, SNU-16, MDA-MB-231, U87MG, H441, H69, and PC3 cells[1]
Concentration:    
Incubation Time:    48 hours
Result:    Inhibited tumor cell proliferation, with IC50 of 19, 9.9, 5223, 1149, 6421, 1851, 21700, 20200, and 10800 nM, respectively.

体内研究
(In Vivo)    
Cabozantinib (100 mg/kg, Orally, once) inhibits MET and VEGFR2 phosphorylation in mice[1].
Cabozantinib (100 mg/kg, Orally, once) significantly increases tumor hypoxia and apoptosis[1].
Cabozantinib (0-60 mg/kg, Orally, once daily for 14 days) inhibits tumor growth in a dose-dependent manner[1].

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

Animal Model:    Female mice bearing MBA-MB-231 tumor (5 per group)[1]
Dosage:    0, 100 mg/kg
Administration:    Orally, once
Result:    Inhibited MET and VEGFR2 phosphorylation.

分子量    
501.51

性状    
Solid

Formula    
C28H24FN3O5

CAS 号    
849217-68-1

中文名称    
卡博替尼

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

储存方式    
4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

溶解性数据    
In Vitro: 
DMSO : 25 mg/mL (49.85 mM; Need ultrasonic)

H2O : < 0.1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.9940 mL    9.9699 mL    19.9398 mL
5 mM    0.3988 mL    1.9940 mL    3.9880 mL
10 mM    0.1994 mL    0.9970 mL    1.9940 mL
*
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 (protect from light)。-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。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 30% polypropylene glycol, 5% Tween-80 and 65% D5W (dextrose 5% water)

Solubility: 10 mg/mL (19.94 mM); Suspended solution; Need ultrasonic

2.
请依序添加每种溶剂： 0.5% CMC/saline water

Solubility: 2.5 mg/mL (4.98 mM); Suspended solution; Need ultrasonic

3.
请依序添加每种溶剂： 5% DMSO    95% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (4.98 mM); Clear solution

4.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 2.08 mg/mL (4.15 mM); Clear solution

5.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: 2.08 mg/mL (4.15 mM); Suspended solution; Need ultrasonic

6.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: ≥ 2.08 mg/mL (4.15 mM); Clear solution
 

参考文献

[1]. Yakes FM, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther, 2011, 10(12), 2298-2308.  [Content Brief] [2]. You WK, et al. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 2011, 71(14), 4758-4768. [Content Brief] [3]. Fuse MA, et al. Combination Therapy With c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells. Mol Cancer Ther. Mol Cancer Ther. 2017 Nov;16(11):2387-2398.  [Content Brief]