Cabozantinib S-malate (XL184 S-malate) is a potent multiple receptor tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl and Flt3 with IC₅₀s of 0.035, 1.3, 4.6, 7 and 11.3 nM, respectively.

Cabozantinib (0.1-0.5μM) inhibits the constitutive and inducible MET phosphorylation and its resultant downstream signaling in all MPNST cells. Cabozantinib (> 0.1μM) elicits a significant MPNST cell growth inhibition; higher Cabozantinib doses are needed to inhibit NSC growth. Cabozantinib treatment blocks HGF-induced MPNST motility and invasion (a similar effect of found on NSC)^[2]. In cellular assays, 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. Cabozantinib also inhibits tubule formation in response to conditioned media derived from cultures of MDA-MB-231 (IC₅₀=5.1 nM), A431 (IC₅₀=4.1 nM), HT1080 (IC₅₀=7.7 nM), and B16F10 (IC₅₀=4.7 nM) cells^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cabozantinib (60 mg/kg, i.p.) decreases the tumor vascularity with reductions ranging from 67% at 3 mg/kg to 83% at 30 mg/kg for 7 days in animals. Tumors in RIP-Tag2 mice treated for 7 days beginning at age 10 weeks are 40% smaller after XL880 and 35% smaller after Cabozantinib, compared to corresponding values for vehicle^[1]. Cabozantinib (30 mg/kg) significantly decreases the microvessel density in mice^[2]. Cabozantinib (100 mg/kg, p.o.) inhibits in vivo stimulation of MET phosphorylation by HGF in liver hepatocytes and VEGF-stimulated phosphorylation of FLK1 with inhibition of both targets sustained through 8 hours postdose. Cabozantinib (100 mg/kg, p.o.) disrupts tumor vasculature and promotes tumor and endothelial cell death. Cabozantinib (1-60 mg/kg, p.o.) inhibits tumor growth and promotes tumor regression in vivo^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

635.59

C₃₂H₃₀FN₃O₁₀

1140909-48-3

卡博替尼苹果酸盐；苹果酸卡博替尼

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 23 mg/mL (36.19 mM)

H₂O : < 0.1 mg/mL (insoluble)

* “≥” means soluble, but saturation unknown.

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。

• [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.

The inhibition profile of cabozantinib against a broad panel of 270 human kinases is determined using luciferase-coupled chemiluminescence, ³³P-phosphoryl transfer, or AlphaScreen technology. Recombinant human full-length, glutathione S-transferase tag, or histidine tag fusion proteins are used, and half maximal inhibitory concentration (IC₅₀) values are determined by measuring phosphorylation of peptide substrate poly (Glu, Tyr) at ATP concentrations at or below the K_m for each respective kinase. The mechanism of kinase inhibition is evaluated using the AlphaScreen Assay by determining the IC₅₀ values over a range of ATP concentrations.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cells are seeded in triplicate overnight in media containing 10% FBS. The next day, cells are treated with serial dilutions of cabozantinib for 48 hours, followed by analysis of proliferation using Cell Proliferation ELISA, BrdUrd.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

H441 cells (3×10⁶) are implanted intradermally into the hind flank and when tumors reach approximately 150 mg, tumor weight is calculated using the formula: (tumor volume=length (mm) × width² (mm²)]/2, mice are randomized (n=5 per group) and orally administered a single 100 mg/kg dose of cabozantinib or vehicle. Tumors are collected at the indicated time points. Pooled tumor lysates are subjected to immunoprecipitation with anti-MET (SC161) and Western blotting with anti-phosphotyrosine MET (pY1230/34/35). After blot stripping, total MET is quantitated as a loading control. In a separate experiment, naive mice (n=5 per group) are administered a single 100 mg/kg dose of cabozantinib or vehicle, followed by intravenous administration of HGF (10 μg per mouse) 10 minutes before liver collection. Analysis of MET phosphorylation in liver lysates is as described above. In a separate experiment, naive mice (n=5 per group) are administered a single 100 mg/kg dose of cabozantinib or vehicle, followed by intravenous administration of VEGF (10 μg per mouse) 30 minutes before lung collection. Pooled lung lysates are subjected to immunoprecipitation with FLK1 (SC6251) and Western blotting with anti-phosphotyrosine (4G10). After blot stripping, total FLK1 is quantitated as a loading control.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.