Cabozantinib-d6 is the deuterated form of Cabozantinib. Cabozantinib is a potent multi-receptor tyrosine kinase inhibitor (antagonist) with IC50s of 0.035, 1.3, 4.6, 7 and 11.3 nM for VEGFR2, c-Met, Kit, Axl and Flt3, respectively.

Physicochemical Properties

Molecular Formula	C28H24FN3O5
Molecular Weight	501.505670547485
Exact Mass	507.207
CAS #	1802168-46-2
Related CAS #	Cabozantinib;849217-68-1
PubChem CID	162640796
Appearance	White to off-white solid powder
LogP	5.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	37
Complexity	795
Defined Atom Stereocenter Count	0
SMILES	C(C1(CC1)C(=O)NC1C=CC(F)=CC=1)(=O)NC1C=CC(OC2=CC=NC3C=C(OC([H])([H])[H])C(OC([H])([H])[H])=CC2=3)=CC=1
InChi Key	ONIQOQHATWINJY-WFGJKAKNSA-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)/i1D3,2D3
Chemical Name	1-N-[4-[6,7-bis(trideuteriomethoxy)quinolin-4-yl]oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
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 Note: This product requires protection from light (avoid light exposure) during transportation and storage.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro

Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].

References

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216. [2]. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 2011, 71(14), 4758-4768. [3]. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther, 2011, 10(12), 2298-2308. [4]. Combination Therapy With c-Met and Src Inhibitors Induces Caspase-Dependent Apoptosis of Merlin-Deficient Schwann Cells and Suppresses Growth of Schwannoma Cells. Mol Cancer Ther. Mol Cancer Ther. 2017 Nov;16(11):2387-2398.

Solubility Data

Solubility (In Vitro)

DMSO : 120 mg/mL (236.43 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (9.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 3 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (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.