Cabozantinib (XL184; BMS907351; Cometriq)

Alias: Cabozantinib; XL-184; BMS-907351; BMS907351; XL184; XL 184; BMS 907351; Cabozantinib free base; trade name Cometriq

Cat No.:V0490 Purity: ≥98%

COA Product Data Instructions for use SDS

Cabozantinib (formerly known as XL-184 or BMS-907351; trade name Cometriq) is a novel, orally bioavailable and potent VEGFR2 inhibitor with anticancer activity.

Cabozantinib (XL184; BMS907351; Cometriq) Chemical Structure CAS No.: 849217-68-1
Product category: VEGFR

This product is for research use only, not for human use. We do not sell to patients.

Size	Price	Stock	Qty
10mg
50mg
100mg
250mg
500mg
Other Sizes

ADD TO CART CHECKOUT BULK INQUIRY

1-708-310-1919 sales@invivochem.com

Other Forms of Cabozantinib (XL184; BMS907351; Cometriq):

Official Supplier of:

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

Cabozantinib (formerly known as XL-184 or BMS-907351; trade name Cometriq) is a novel, orally bioavailable and potent VEGFR2 inhibitor with anticancer activity. Its IC50 of 0.035 nM is sufficient to inhibit VEGFR2. This inhibitor of multiple receptor tyrosine kinase (RTK) also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL, with IC50 values in cell-free assays of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, and 7 nM, respectively. A number of tyrosine receptor kinases are strongly bound by capozantinib and inhibited by it. The FDA in the United States approved cabotezantinib in November 2012 to treat medullary thyroid cancer.

Biological Activity I Assay Protocols (From Reference)

Targets

VEGFR2 (IC50 = 0.035 nM); Flt-4 (IC50 = 6 nM); Flt-1 (IC50 = 12 nM); Met (IC50 = 1.3 ± 1.2 nM)

ln Vitro

XL184 exhibits low inhibitory activity against FGFR1 with an IC50 of 5.294 μM and weak inhibitory activity against RON and PDGFRβ, with IC50s of 124 nM and 234 nM, respectively.[1] XL184 can effectively suppress constitutive and inducible Met phosphorylation and the downstream signaling it causes in MPNST cells, as well as block HGF-induced MPNST cell migration and invasion, even at low concentrations (0.1–0.5 μM). In cytokine-stimulated human umbilical vein endothelial cells (HUVECs), XL184 also significantly inhibits the phosphorylation of Met and VEGFR2. At 0.1 μM, XL-184 has no discernible effect on MPNST cell growth; however, at 5–10 μM, XL184 significantly inhibits MPNST cell growth.[2]

ln Vivo

XL184 treatment at 30 mg/kg in RIP-Tag2 mice with spontaneous pancreatic islet tumors disrupts 83% of the tumor vasculature, decreases pericytes and empty basement membrane sleeves, causes widespread intratumoral hypoxia and extensive tumor cell apoptosis, and slows the tumor vasculature's regrowth after stopping the drug. This is different from XL999, which blocks VEGFR but not c-Met, resulting in only 43% reduction in vascularity, indicating that simultaneous inhibition of VEGFR and other functionally relevant receptor tyrosine kinases (RTK) amplifies the inhibition of angiogenesis. Moreover, XL184 lessens metastasis and the invasiveness of original tumors.[1] At 30 mg/kg/day, XL184 dramatically inhibits the growth and metastasis of human MPNST xenografts in SCID mice.[2] In models of breast, lung, and glioma tumors, the administration of XL184 results in a dose-dependent inhibition of tumor growth, along with a decrease in the proliferation of tumor and endothelial cells and an increase in apoptosis. For MDA-MB-231 tumor-bearing mice and C6 tumor-bearing rats, a single oral dosage of XL184 at 100 mg/kg and 10 mg/kg, respectively, is sufficient to cause long-term tumor growth inhibition.[3]

Enzyme Assay

In addition to inhibiting c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 values of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM, and 7 nM, respectively, cabotinib (XL184, BMS-907351) is a potent inhibitor of VEGFR2.

Cell Assay

For 48 hours, different XL184 concentrations are applied to the cells. Using the CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay kit, MTS assays are used to measure cell growth. The wavelength at which absorbance is measured is 490 nm, and the treated cells' absorbance values are expressed as a percentage of the untreated cells' absorbance.

Animal Protocol

RIP-Tag2 transgenic mice in a C57BL/6 background with spontaneous pancreatic islet tumors
~60 mg/kg
Oral gavage

References

[1]. Cancer Res . 2011 Jul 15;71(14):4758-68.

[2]. Clin Cancer Res . 2011 Jun 15;17(12):3943-55.

[3]. Mol Cancer Ther . 2011 Dec;10(12):2298-308.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C28H24FN3O5
Molecular Weight	501.51
Exact Mass	501.17
Elemental Analysis	C, 67.06; H, 4.82; F, 3.79; N, 8.38; O, 15.95
CAS #	849217-68-1
Related CAS #	Cabozantinib S-malate;1140909-48-3;Cabozantinib-d6;1802168-46-2;Cabozantinib hydrochloride;1817759-42-4;Cabozantinib-d4;1802168-53-1
Appearance	white solid powder
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
InChi Key	ONIQOQHATWINJY-UHFFFAOYSA-N
InChi Code	InChI=1S/C28H24FN3O5/c1-35-24-15-21-22(16-25(24)36-2)30-14-11-23(21)37-20-9-7-19(8-10-20)32-27(34)28(12-13-28)26(33)31-18-5-3-17(29)4-6-18/h3-11,14-16H,12-13H2,1-2H3,(H,31,33)(H,32,34)
Chemical Name	1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Synonyms	Cabozantinib; XL-184; BMS-907351; BMS907351; XL184; XL 184; BMS 907351; Cabozantinib free base; trade name Cometriq
HS Tariff Code	2934.99.9001
Storage	Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility Data

Solubility (In Vitro)

DMSO: ~100 mg/mL (~199.4 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

Solubility (In Vivo)

2%DMSO+30%PEG 300+5%Tween 80+ddH2O: 2mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9940 mL	9.9699 mL	19.9398 mL
	5 mM	0.3988 mL	1.9940 mL	3.9880 mL
	10 mM	0.1994 mL	0.9970 mL	1.9940 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculate Reset

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate Reset

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculate Reset

Calculation results

Working concentration： mg/mL；

Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O，mix and clarify.

Note： (1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04804813	Active Recruiting	Drug: Cabozantinib	Renal Cell Carcinoma	Takeda	March 29, 2021
NCT04868773	Active Recruiting	Drug: Cabozantinib Drug: TAS-102	CRC Metastatic Cancer	University of California, Irvine	July 16, 2021	Phase 1
NCT04416646	Active Recruiting	Drug: Cabozantinib	Renal Cell Carcinoma	Istituto Oncologico Veneto IRCCS	February 27, 2019
NCT04400474	Active Recruiting	Drug: Cabozantinib 40 mg	Adenocarcinoma Paraganglioma	Grupo Espanol de Tumores Neuroendocrinos	October 7, 2020	Phase 2
NCT05200143	Active Recruiting	Drug: Ipilimumab Drug: Cabozantinib	Refractory Cutaneous Melanoma	Providence Health & Services	June 8, 2022	Phase 2

Biological Data

The multi-tyrosine kinase inhibitor, XL184, targeting MET and VEGFR2 abrogates MPNST migration, invasion, and angiogenesis. Clin Cancer Res. 2011 Jun 15;17(12):3943-55.
XL184 abrogates local and metastatic MPNST growth in vivo. Clin Cancer Res. 2011 Jun 15;17(12):3943-55.