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Cabozantinib

Cabozantinib

品 牌 MCE
C A S 号 849217-68-1
货 号 HY-13016
规 格 5mg
价 格(元) 780.00
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货号 规格 价格
HY-13016 5mg 780.00
HY-13016 10mg 1100.00
HY-13016 50mg 2850.00
HY-13016 100mg 4000.00
HY-13016 200mg 6500.00

产品说明


Cabozantinib (卡博替尼; XL184, BMS-907351) 是高活性VEGFR2抑制剂,IC50为0.035 nM,还能抑制c-Met,Ret,Kit,Flt-1/3/4,Tie2和AXL,IC50分别为1.3 nM,4 nM,4.6 nM,12 nM/11.3 nM/6 nM,14.3 nM和7 nM。



Cabozantinib的生物活性


Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
IC50 value: 0.035 nM [1]
Target: VEGFR2
in vitro: XL184 has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectivey, and has low activity against FGFR1 with IC50 of 5.294 μM [1]. XL184 at low concentration (0.1-0.5 μM) is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signaling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. XL184 also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although XL-184 has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth [2].
in vivo: XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows regrowth of the tumor vasculature after drug withdrawal, more significantly compared with XL999 that blocks VEGFR but not c-Met, leading to only 43% reduction in vascularity, suggesting that concurrent inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies angiogenesis inhibition. XL184 also decreases invasiveness of primary tumors and reduces metastasis [1]. XL184 at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice [2]. Administration of XL184 induces dose-dependent inhibition of tumor growth in breast, lung, and glioma tumor models, in association with decreased tumor and endothelial cell proliferation as well as increased apoptosis. A single oral dose of XL184 is sufficient to induce sustained tumor growth inhibition in MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats at 100 mg/kg and 10 mg/kg, respectively [3].

化学信息


分子量 501.51 储存条件 参考CoA中推荐的条件进行储存。
分子式 C₂₈H₂₄FN₃O₅
CAS号 849217-68-1
溶剂/溶解度 DMSO: ≥ 30 mg/mL

相关文献


[1]. You WK, et al. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 2011, 71(14), 4758-4768.
[2]. Torres KE, et al. Activated MET is a molecular prognosticator and potential therapeutic target for malignant peripheral nerve sheath tumors. Clin Cancer Res, 2011, 17(12), 3943-3955.
[3]. 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.