Cabozantinib (XL184)

Catalog No.S1119 Batch:S111911

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Technical Data

Formula

C28H24FN3O5
Molecular Weight 501.51 CAS No. 849217-68-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (199.39 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Cabozantinib (XL184) 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 in cell-free assays, respectively. Cabozantinib induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signaling pathway.
Targets
VEGFR2/KDR [1]
(Cell-free assay)		 c-Met [1]
(Cell-free assay)		 Axl [1]
(Cell-free assay)
0.035 nM 1.3 nM 7 nM
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]

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    ST88-14, STS26T, and MPNST724

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    48 hours

  • Method

    Cells are exposed to various concentrations of XL184 for 48 hours. Cell growth is determined by MTS assays using CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit. Absorbance is measured at a wavelength of 490 nm, and the absorbance values of treated cells are presented as a percentage of the absorbance of untreated cells.
Animal Study:

[1]
  • Animal Models

    RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors

  • Dosages

    ~60 mg/kg

  • Administration

    Oral gavage

Customer Product Validation

Data from [Data independently produced by Cancer Discov, 2014, 4(7), 816-27]

Data from [Cell Death Dis, 2014, 5, e1471]

Data from [Data independently produced by Liver Int, 2014, 10.1111/liv.12524]

, , Christina W Yde/CDM Danish Cancer Society Research Center Denmark

Selleck's Cabozantinib (XL184) has been cited by 158 publications

Construction of disulfidptosis-based immune response prediction model with artificial intelligence and validation of the pivotal grouping oncogene c-MET in regulating T cell exhaustion [ Front Immunol, 2024, 15:1258475] PubMed: 38352883
Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations [ Nat Cancer, 2023, 4(9):1345-1361] PubMed: 37743366
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] PubMed: 36736316
Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519 [ Biomed Pharmacother, 2023, 164:115002] PubMed: 37311277
Impact of tumor suppressor genes inactivation on the multidrug resistance phenotype of hepatocellular carcinoma cells [ Biomed Pharmacother, 2023, 165:115209] PubMed: 37499450
Anti-hepatocellular carcinoma activity of the cyclin-dependent kinase inhibitor AT7519 [ Biomed Pharmacother, 2023, 164:115002] PubMed: 37311277
Relevance of the organic anion transporting polypeptide 1B3 (OATP1B3) in the personalized pharmacological treatment of hepatocellular carcinoma [ Biochem Pharmacol, 2023, 214:115681] PubMed: 37429423
Role of organic cation transporter 3 (OCT3) in the response of hepatocellular carcinoma to tyrosine kinase inhibitors [ Biochem Pharmacol, 2023, 217:115812] PubMed: 37722628
Validation of miRNAs as diagnostic and prognostic biomarkers, and possible therapeutic targets in medullary thyroid cancers [ Front Endocrinol (Lausanne), 2023, 14:1151583] PubMed: 37361540
Cabozantinib inhibits HBV-RNA transcription by decreasing STAT3 binding to the enhancer region of cccDNA [ Hepatol Commun, 2023, 10.1097/HC9.0000000000000313] PubMed: 37938099

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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