Cabozantinib malate (XL184)

Catalog No.S4001

For research use only.

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.

Cabozantinib malate (XL184) Chemical Structure

CAS No. 1140909-48-3

Selleck's Cabozantinib malate (XL184) has been cited by 90 publications

Purity & Quality Control

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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)
Click to View More Targets
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]

Assay
Methods Test Index PMID
Western blot pROS1 / pERK / pSHP2 / p-STAT3 / p-AKT ; p-MET / MET / p-ERK5 / ERK5 / DCLK1 26673800 28560410
Growth inhibition assay Cell viability 28560410
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 Research:

[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 Research:

[1]

  • Animal Models: RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
  • Dosages: ~60 mg/kg
  • Administration: Oral gavage

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
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

15 mg/mL

Chemical Information

Molecular Weight 635.59
Formula

C28H24FN3O5.C4H6O5

CAS No. 1140909-48-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F.C(C(C(=O)O)O)C(=O)O

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05048212 Not yet recruiting Drug: Nivolumab|Drug: Ipilimumab|Drug: Cabozantinib Brain Metastases|Renal Cell Carcinoma M.D. Anderson Cancer Center|Exelixis|Bristol-Myers Squibb February 28 2022 Phase 2
NCT05182164 Not yet recruiting Drug: Association of pembrolizumab + cabozantinib Soft Tissue Sarcoma Adult|Advanced Soft-tissue Sarcoma|Ewing Sarcoma|Osteosarcoma|Undifferentiated Pleomorphic Sarcoma Institut Bergonié|Ipsen|MSD France December 31 2021 Phase 2
NCT05100082 Recruiting Drug: Cabozantinib Hepatocellular Cancer Takeda November 17 2021 --
NCT05135975 Active not recruiting Drug: Cabozantinib Neuroblastoma|CNS Tumor|Sarcoma Nationwide Children''s Hospital|Exelixis October 18 2021 Phase 2
NCT05048901 Not yet recruiting Drug: Cabozantinib|Drug: Lanreotide Neuroendocrine TumorsGastroenteropancreatic National Health Research Institutes Taiwan|National Taiwan University Hospital|Taipei Veterans General Hospital Taiwan|Mackay Memorial Hospital|Tri-Service General Hospital|Changhua Christian Hospital|China Medical University Hospital|National Cheng-Kung University Hospital|Kaohsiung Medical University Chung-Ho Memorial Hospital September 30 2021 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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