产品说明书

Cabozantinib

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Chemical Structure| 849217-68-1 同义名 : XL184;BMS-907351
CAS号 : 849217-68-1
货号 : A200488
分子式 : C28H24FN3O5
纯度 : 98%
分子量 : 501.506
MDL号 : -
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(49.85 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 4.6 mg/mL clear

PO 0.5% CMC-Na 46 mg/mL suspension

生物活性
靶点

  • VEGFR2

    VEGFR2/KDR, IC50:0.035 nM
描述 The inhibition of VEGF/VEGFR, as well as HGF/c-Met pathway contributes to tumor growth, angiogenesis, invasiveness and metastasis in preclinical studies. Cabozantinib is a potent VEGFR2 inhibitor with IC50 value of 0.035nM, as well as shows inhibitory effect on c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 values of 1.3nM, 4nM, 4.6nM, 12nM/11.3nM/6nM, 14.3nM and 7nM (measured by kinase activity), respectively[1]. Treatment with Cabozantinib dose-dependently inhibited HGF-induced p-Met at concentration>0.05μM and its downstream p-AKT at concentration>0.1μM in MPNST724 cells, as well as at concentration of 1μM in HUVECs, 0.5μM in ST88 and STS26T cells. The inhibition of VEGFR-2 by Cabozantinib can be observed, as decreased p-VEGFR2, at concentration>0.5μM in HUVECs. Cabozantinib inhibited HGF-induced MPNST cell migration and invasion at 0.5μM for 4h. As prediction by inhibition of Cabozantinib on VEGFR2 and c-Met, Cabozantinib showed potent anti-angiogenesis effect in vivo. The in vivo gel-foam suggested that angiogenesis induced by HGF, VEGF or both decreased (measured based on CD31) by administration of 30mg/kg Cabozantinib for 10 days[2]. Oral treatment with Cabozantinib for 7 days reduced tumor vascularity by 67% at 3mg/kg and by 83% at 30mg/kg in RIP-Tag2 tumors[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
E98NT 0.01-10 μM Growth Inhibition Assay IC50=89 nM 23484006
H441 Growth Inhibition Assay IC50=21700 nM 21926191
H69 Growth Inhibition Assay IC50=20200 nM 21926191
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.99mL

0.40mL

0.20mL

9.97mL

1.99mL

1.00mL

19.94mL

3.99mL

1.99mL
参考文献

[1]You WK, Sennino B, et al. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res. 2011;71(14):4758-68.

[2]Torres KE, Zhu QS, et al. Activated MET is a molecular prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumors. Clin Cancer Res. 2011;17(12):3943-55.

[3]Nguyen HM, Ruppender N, et al. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling. PLoS One. 2013;8(10):e78881.

[4]Navis AC, Bourgonje A, et al. Effects of dual targeting of tumor cells and stroma in human glioblastoma xenografts with a tyrosine kinase inhibitor against c-MET and VEGFR2. PLoS One. 2013;8(3):e58262.

[5]Haider MT, Hunter KD, et al. Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo. Bone. 2015 Dec;81:581-592.

[6]Yang S, Zhang X, et al. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway. Cancer Gene Ther. 2019 Jun 11.

[7]XL 184