Cabozantinib (XL184, BMS-907351)

Catalog No.S1119
5 5 11 Product Citations

Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and 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, respectively.

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In DMSO USD 220 In stock
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Cabozantinib (XL184, BMS-907351) Chemical Structure

Cabozantinib (XL184, BMS-907351) Chemical Structure
Molecular Weight: 501.51

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

Related Compound Libraries

Cabozantinib (XL184, BMS-907351) is available in the following compound libraries:

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Product Information

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  • Research Area
  • Inhibition Profile

Product Description

Biological Activity

Description Cabozantinib (XL184, BMS-907351) is a potent VEGFR2 inhibitor with IC50 of 0.035 nM and 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, respectively.
Targets VEGFR2/KDR [1] c-Met [1] Kit [1] VEGFR3/FLT4 [1] Axl [1]

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IC50 0.035 nM 1.3 nM 4.6 nM 6.0 nM 7.0 nM
In vitro XL184 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] XL184 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. XL184 also induces marked inhibition of Met and VEGFR2 phosphorylation in cytokine-stimulated human umbilical vein endothelial cells (HUVECs). Although XL-184 has no significant effect on MPNST cell growth at 0.1 μM, XL184 at 5-10 μM significantly inhibits the MPNST cell growth. [2]
In vivo XL184 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. XL184 also decreases invasiveness of primary tumors and reduces metastasis. [1] XL184 at 30 mg/kg/day significantly abrogates human MPNST xenografts growth and metastasis in SCID mice. [2] Administration of XL184 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 XL184 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]
Features

Protocol(Only for 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 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
Formulation Suspended at a concentration of 5 mg/mL in sterile saline or water
Dosages ~60 mg/kg
Administration Oral gavage
Solubility 30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] You WK, et al. Cancer Res, 2011, 71(14), 4758-4768.

[2] Torres KE, et al. Clin Cancer Res, 2011, 17(12), 3943-3955.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2014-12-20)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02315430 Not yet recruiting Fallopian Tube Clear Cell Adenocarcinoma|Malignant Ovarian Clear Cell Tumor|Progressive Disease|Recurrent Fallopian Tube Carcinoma|Recurrent Ovaria  ...more Fallopian Tube Clear Cell Adenocarcinoma|Malignant Ovarian Clear Cell Tumor|Progressive Disease|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma National Cancer Institute (NCI) April 2015 Phase 2
NCT02315430 Not yet recruiting Fallopian Tube Clear Cell Adenocarcinoma|Malignant Ovarian Clear Cell Tumor|Progressive Disease|Recurrent Fallopian Tube Carcinoma|Recurrent Ovaria  ...more Fallopian Tube Clear Cell Adenocarcinoma|Malignant Ovarian Clear Cell Tumor|Progressive Disease|Recurrent Fallopian Tube Carcinoma|Recurrent Ovarian Carcinoma|Recurrent Primary Peritoneal Carcinoma National Cancer Institute (NCI) April 2015 Phase 2
NCT02302833 Not yet recruiting Neuroendocrine Tumors M.D. Anderson Cancer Center|Exelixis March 2015 --
NCT02302833 Not yet recruiting Neuroendocrine Tumors M.D. Anderson Cancer Center|Exelixis March 2015 --
NCT02308943 Not yet recruiting Adult Solid Neoplasm|Malignant Reproductive System Neoplasm|Malignant Urinary System Neoplasm|Metastatic Malignant Neoplasm|Metastatic Urothelial C  ...more Adult Solid Neoplasm|Malignant Reproductive System Neoplasm|Malignant Urinary System Neoplasm|Metastatic Malignant Neoplasm|Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter|Progressive Neoplastic Disease|Recurrent Bladder Carcinoma|Recurrent Urethra Carcinoma|Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter|Regional Urothelial Carcinoma of the Renal Pelvis and Ureter|Stage III Bladder Urothelial Carcinoma|Stage III Urethral Cancer|Stage IV Bladder Urothelial Carcinoma|Stage IV Urethral Cancer|Urethral Urothelial Carcinoma National Cancer Institute (NCI) January 2015 Phase 1

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Chemical Information

Download Cabozantinib (XL184, BMS-907351) SDF
Molecular Weight (MW) 501.51
Formula

C28H24FN3O5

CAS No. 849217-68-1
Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms
Solubility (25°C) * In vitro DMSO 100 mg/mL (199.39 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% propylene glycol, 5% Tween 80, 65% D5W 30 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.
Chemical Name N-(4-(6,7-dimethoxyquinolin-4-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Research Area

Customer Reviews (4)


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Rating
Source Cancer Discov 2014 4(7), 816-27. Cabozantinib (XL184, BMS-907351) purchased from Selleck
Method Western blot
Cell Lines A-375 melanoma cells
Concentrations 3 uM
Incubation Time
Results XL184 combined with PLX4720, compared to PLX 4720 alone, abrogated AXL-mediated induction of AKT phosphorylation and rescue of ERK phosphorylation but had no effect on AKT or ERK levels in A-375 cell lines.

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Rating
Source Cell Death Dis 2014 5, e1471. Cabozantinib (XL184, BMS-907351) purchased from Selleck
Method MTT assay, Spheroid formation assay
Cell Lines GCTB stromal cells
Concentrations 10 uM
Incubation Time 7 days
Results Cabozantinib significantly reduced the cell number and viability, whereas methotrexate was minimally effective as evident from morphologic changes and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To investigate whether cabozantinib affects the self-renewal potential, spheroidal-growing cells were left untreated or were treated with cabozantinib and methotrexate, respectively. Seven days later, the spheroids were photographed, and their volumes were determined.

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Rating
Source Liver Int 2014 10.1111/liv.12524. Cabozantinib (XL184, BMS-907351) purchased from Selleck
Method Fluorescence microscopy, flow cytometric analysis
Cell Lines HepG2/adr cells
Concentrations 0.75, 1.5, 5 uM
Incubation Time 3 h
Results As shown in A, the treatment of HepG2/adr cells with 1.5 uM cabozantinib significantly increased the intracellular accumulation of Dox and Rho123, as indicated by stronger red and green fluorescence intensity, respectively, compared with the corresponding negative controls. The fluorescence index of Dox was increased by 1.53- and 2.17-fold in HepG2/adr cells in the presence of 0.75 and 1.5 uM of cabozantinib respectively. The same doses of cabozantinib increased the fluorescence index of Rho123 2.16- and 3.43-fold in HepG2/adr cells.

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Rating
Source Christina W Yde/CDM Danish Cancer Society Research Center Denmark. Cabozantinib (XL184, BMS-907351) purchased from Selleck
Method Cell growth assay
Cell Lines MCF-7 breast cancer cells
Concentrations 0-1.5 μM
Incubation Time 5 d
Results XL-184 potently inhibited the survival of MCF-7 cells in a dose-dependent manner.

Product Citations (11)

Tech Support & FAQs

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