Cabozantinib malate

Catalog No.S4001 Batch:S400103

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Technical Data

Formula

C28H24FN3O5.C4H6O5
Molecular Weight 635.59 CAS No. 1140909-48-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (157.33 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 malate (XL184) is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret (c-Ret), Kit (c-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 malate (XL184) induces apoptosis.
Targets
VEGFR2/KDR [1]
(Cell-free assay)		 c-Met [1]
(Cell-free assay)		 RET [1]
(Cell-free assay)		 Kit [1]
(Cell-free assay)		 Flt-4 [1]
(Cell-free assay)		 View More
0.035 nM 1.3 nM 4 nM 4.6 nM 6 nM
In vitro Cabozantinib 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] Cabozantinib 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. Cabozantinib also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although Cabozantinib has no significant effect on MPNST cell growth at 0.1 μM, Cabozantinib at 5-10 μM significantly inhibits the MPNST cell growth. [2]
In vivo Cabozantinib 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. Cabozantinib also decreases invasiveness of primary tumors and reduces metastasis. [1] Cabozantinib at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. [2] Administration of Cabozantinib 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 Cabozantinib 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 Cabozantinib 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 [Cancer Discov, 2014, 4(7), 816-27]

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

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

Data from [Data independently produced by Mol Imaging, 2014, 10.2310/7290.2014.00026]

Selleck's Cabozantinib malate has been cited by 105 publications

A subset of VEGFR-TKIs activates AMPK in LKB1-mutant lung cancer [ Cancer Sci, 2023, 114(4):1651-1662] PubMed: 36459496
Identification of therapeutic sensitivities in a spheroid drug combination screen of Neurofibromatosis Type I associated High Grade Gliomas [ PLoS One, 2023, 18(2):e0277306] PubMed: 36730269
Rapid Profiling of Tumor-Immune Interaction Using Acoustically Assembled Patient-Derived Cell Clusters [ Adv Sci (Weinh), 2022, e2201478] PubMed: 35611994
CIC-mediated modulation of MAPK signaling opposes receptor tyrosine kinase inhibitor response in kinase-addicted sarcoma [ Cancer Res, 2022, canres.1397.2021] PubMed: 35074756
Targeting PEA3 transcription factors to mitigate small cell lung cancer progression [ Oncogene, 2022, 10.1038/s41388-022-02558-6] PubMed: 36509998
Plasma extracellular vesicle long RNA profiles in the diagnosis and prediction of treatment response for breast cancer [ Cancers (Basel), 2022, 14(7)1683] PubMed: 35406455
MET Exon 14 Splice-Site Mutations Preferentially Activate KRAS Signaling to Drive Tumourigenesis [ Cancers (Basel), 2022, 14(6)1378] PubMed: 35326531
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746
Sprouting Angiogenesis in Human Pituitary Adenomas [ Front Oncol, 2022, 12:875219] PubMed: 35600354
Blockade of CD47 enhances the antitumor effect of macrophages in renal cell carcinoma through trogocytosis [ Sci Rep, 2022, 12(1):12546] PubMed: 35869130

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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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