Cabozantinib malate

Catalog No.S4001 Batch:S400104

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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
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.)

Preparing Stock Solutions

Biological Activity

Description Cabozantinib malate (XL184) is the malate of Cabozantinib, a potent VEGFR2 inhibitor with an IC50 of 0.035 nM and also inhibits c-Met, Ret (c-Ret), Kit (c-Kit), Flt-1/3/4, Tie2, and AXL with an 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. This compound induces apoptosis.
Targets
VEGFR2/KDR
(Cell-free assay)		 c-Met
(Cell-free assay)		 RET
(Cell-free assay)		 Kit
(Cell-free assay)		 Flt-4
(Cell-free assay)		 View More
0.035 nM 1.3 nM 4 nM 4.6 nM 6 nM
In vitro Cabozantinib malate has weak inhibitory activity against RON and PDGFRβ with IC50 of 124 nM and 234 nM, respectively, and has low activity against FGFR1 with IC50 of 5.294 μM. This compound at low concentration (0.1-0.5 μM) is sufficient to induce marked inhibition of constitutive and inducible Met phosphorylation and its resultant downstream signalling in MPNST cells, and inhibit HGF-induced MPNST cell migration and invasion. It also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although this chemical has no significant effect on MPNST cell growth at 0.1 μM, it at 5-10 μM significantly inhibits the MPNST cell growth.
In Vivo Cabozantinib malate treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumours disrupts 83% of the tumour vasculature, reduces pericytes and empty basement membrane sleeves, causes widespread intratumoural hypoxia and extensive tumour cell apoptosis, and slows regrowth of the tumour 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. This compound also decreases invasiveness of primary tumours and reduces metastasis. This chemical at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. Administration of this compound induces dose-dependent inhibition of tumour growth in breast, lung, and glioma tumour models, in association with decreased tumour and endothelial cell proliferation as well as increased apoptosis. A single oral dose of this chemical is sufficient to induce sustained tumour growth inhibition in MDA-MB-231 tumour-bearing mice and C6 tumour-bearing rats at 100 mg/kg and 10 mg/kg, respectively.

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 malate 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

References

  • https://pubmed.ncbi.nlm.nih.gov/21613405/
  • https://pubmed.ncbi.nlm.nih.gov/21540237/
  • https://pubmed.ncbi.nlm.nih.gov/21926191/

Customer Product Validation

Effects of AXL inhibitors on induction of pAKT and rescue of pERK following AXL overexpression. R428, 500 nmol/L; XL184, 3 umol/L; XL880, 100 nmol/L; in the presence or absence of 2 umol/L PLX4720. shAXL is a positive control.

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

Cabozantinib reduces viability and spheroid and colony formation of GCTB stromal cells. (a) Adherent-growing GCTB stromal cells derived from three different patients were left untreated (CO) or were treated with cabozantinib (10 uM, XL184) or methotrexate (100 uM, MTX). Seventy-two hours later, the viability was measured by the MTT assay, and the control was set to 100%. (b) Spheroidal cultures were established as described in b. After spheroid formation, the cells were left untreated or were treated as described above. Seven days later, spheroids were photographed, and the number and volume of spheroids (spheroid surface) were determined. The data shown are the mean盨.D. (*P<0.05; **P<0.01).

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

The effect of cabozantinib on the accumulation of Dox and Rho123. (A) Fluorescence microscopy observation of the accumulation of Dox and Rho123. The scale bars represent 100 uM. (B) The accumulation of Dox and Rho123 was measured by flow cytometric analysis. The data were analysed using Kaluza software and are presented as fold-change in fluorescence intensity relative to the control HepG2/adr cells. The results are shown as the mean ± SD of three independent trials. *P < 0.05 vs. the control group.

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

A summary of the postcabozantinib (Cabo.) changes in bone-seeking radionuclide uptake at sites of remodeling bone. C, A line graph of the SUV mean for <sup>99m</sup> Tc-MDP uptake at the site of the fracture in the tibia shows the impact of cabozantinib therapy on radionuclide accumulation. Animals were treated once daily with cabozantinib at 30 mg/kg 1 day after the first SPECT scan. D, Representative maximum-intensity projection (MIP) images whose intensities were manually gated to provide a clear view of radionuclide uptake at the fracture site and the nearby anatomy. Quantification was not conducted using the MIP images; the MIP images are merely provided to show a global view of <sup>99m</sup>Tc-MDP distribution in the skeleton while underscoring the foci of high radionuclide uptake at the fracture. Unfortunately, centering the images on the slices with the fracture excluded the rest of the anatomy, resulting in images that are difficult to interpret visually. *p< .01. Rx 5 treatment.

Data from [ Mol Imaging , 2014 , 10.2310/7290.2014.00026 ]

Sellecks Cabozantinib malate Has Been Cited by 110 Publications

Biofabrication of pheochromocytoma and paraganglioma tumor organoids and assessment of response to systemic therapy [ Sci Rep, 2025, 15(1):35889] PubMed: 41087622
Tyrosine kinase inhibitors affect sweet taste and dysregulate fate selection of specific taste cell subtypes via KIT inhibition [ bioRxiv, 2025, 2025.08.15.670608] PubMed: 40894646
Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation [ Nat Neurosci, 2024, 10.1038/s41593-024-01604-8] PubMed: 38528202
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271
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

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