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Cabozantinib malate (XL184)

Name: Cabozantinib malate (XL184)
Brand: Selleck Chemicals
SKU: S4001
Rating: 5 (90 reviews)

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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VEGFR Signaling Pathway Map

Biological Activity

Description

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	Click to View More Targets

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

References

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. Click to purchase: Tween 80	15 mg/mL

Chemical Information

Molecular Weight	635.59
Formula	C₂₈H₂₄FN₃O₅.C₄H₆O₅
CAS No.	1140909-48-3
Storage	3 years	-20°C	powder
Storage	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

Download Cabozantinib malate (XL184) SDF

In vivo Formulation Calculator (Clear solution)

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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.

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Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

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)

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