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
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 A potent VEGFR2 inhibitor with IC50 of 0.035 nM, Cabozantinib (XL184) 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. It induces PUMA-dependent apoptosis in colon cancer cells via AKT/GSK-3β/NF-κB signalling pathway.
Targets
VEGFR2/KDR
(Cell-free assay)		 c-Met
(Cell-free assay)		 Axl
(Cell-free assay)
0.035 nM 1.3 nM 7 nM
In vitro Cabozantinib (XL184) 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. At low concentration (0.1-0.5 μM), it 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. This compound also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although it has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth.
In Vivo Cabozantinib (XL184) 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. At 30 mg/kg/day, it significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. Administration of XL184 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 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 (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

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 ]

<p>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 MD. (*P<0.05; **P<0.01).</p>

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 ]

<p>Inhibition of breast cancer cell growth using XL184. MCF-7 breast cancer cells were treated with increasing concentrations of XL-184 for 5 days. Cell number was measured  using a colorimetric growth assay (crystal violet stain) and expressed relative to DMSO treated control cells.</p><p> </p>

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

Sellecks Cabozantinib (XL184) Has Been Cited by 169 Publications

S100P is a ferroptosis suppressor to facilitate hepatocellular carcinoma development by rewiring lipid metabolism [ Nat Commun, 2025, 16(1):509] PubMed: 39779666
ARID1A loss enhances sensitivity to c-MET inhibition by dual targeting of GPX4 and iron homeostasis, inducing ferroptosis [ Cell Death Differ, 2025, 10.1038/s41418-025-01510-x] PubMed: 40369167
Inhibition of TFF3 synergizes with c-MET inhibitors to decrease the CSC-like phenotype and metastatic burden in ER+HER2+ mammary carcinoma [ Cell Death Dis, 2025, 16(1):76] PubMed: 39920140
Relevance of transportome among the mechanisms of chemoresistance in hepatoblastoma [ Biochem Pharmacol, 2025, 237:116914] PubMed: 40185314
A Robust Marine Collagen Peptide-Agarose 3D Culture System for In Vitro Modeling of Hepatocellular Carcinoma and Anti-Cancer Therapeutic Development [ Mar Drugs, 2025, 23(10)386] PubMed: 41149589
Characterisation of an autochthonous mouse ccRCC model of immune checkpoint inhibitor therapy resistance [ Sci Rep, 2025, 15(1):19818] PubMed: 40473819
Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3 [ Biomed Pharmacother, 2024, 180:117533] PubMed: 39405909
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
Novel therapeutic strategies targeting bypass pathways and mitochondrial dysfunction to combat resistance to RET inhibitors in NSCLC [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(6):167249] PubMed: 38768929
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271

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