Cabozantinib HCl (XL184 hydrochloride; BMS907351; Cometriq) is an orally bioavailable and potent VEGFR2 inhibitor with anticancer activity. It inhibits VEGFR2 with an IC50 of 0.035 nM. It is a multiple receptor tyrosine kinase (RTK) inhibitor that 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 in cell-free assays, respectively. Cabozantinib strongly binds to and inhibits several tyrosine receptor kinases. Cabozantinib was approved by the U.S. FDA in November 2012 for the treatment of medullary thyroid cancer.
Physicochemical Properties
| Molecular Weight | 537.966609716415 |
| Exact Mass | 537.146 |
| CAS # | 1817759-42-4 |
| Related CAS # | Cabozantinib;849217-68-1 |
| PubChem CID | 122573030 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 38 |
| Complexity | 795 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | LCNVAOXPKXBXEH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C28H24FN3O5.ClH/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);1H |
| Chemical Name | 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide;hydrochloride |
| 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) |
Biological Activity
| ln Vitro | Cabozantinib hydrochloride, with IC50 values of 7.8, 1.9, 5.0, 7.5, and 42 μM, respectively, suppresses the phosphorylation of MET and VEGFR2, as well as KIT, FLT3, and AXL [1]. In HMVEC, MDA-MB-231, A431, HT1080, and B16F10 cells, respectively, capozantinib hydrochloride (4.6 nM) suppresses renal tubule development without exhibiting any signs of cytotoxicity. both 4.7 and 7.7 nM[1]. Inhibiting cell migration and invasion, cabotezantinib hydrochloride (0-370 nM, 24 hours) is used [1]. Inhibiting the growth of tumor cells in different types of tumors is possible with cabotinib hydrochloride (48 hours) [1]. |
| ln Vivo | Cabozantinib hydrochloride (100 mg/kg, orally, once) suppresses MET and VEGFR2 phosphorylation in mice [1]. Cabozantinib hydrochloride (100 mg/kg, orally, once) dramatically enhances tumor hypoxia and apoptosis [1]. Cabozantinib hydrochloride (0-60 mg/kg, orally, once daily for 14 days) suppresses tumor development in a dose-dependent manner [1]. |
| Cell Assay |
Cell Proliferation Assay Cell Types: SNU-5, Hs746T, SNU-1, SNU-16, MDA-MB-231, U87MG, H441, H69 and PC3 cells [1] Tested Concentrations: Incubation Duration: 48 hrs (hours) Experimental Results: Inhibition of tumor cell proliferation , IC50 are 19, 9.9, 5223, 1149, 6421, 1851, 21700, 20200 and 10800 nM respectively. Cell migration assay Cell Types: B16F10 cells [1] Tested Concentrations: 0, 41, 123 and 370 nM Incubation Duration: 24 hrs (hours) Experimental Results: Effectively inhibited HGF-induced B16F10 cell migration (IC50 = 31 nM). Cell invasion assay Cell Types: B16F10 cells [1] Tested Concentrations: 0, 1.5, 14 and 123 nM Incubation Duration: 24 hrs (hours) Experimental Results: Effectively inhibited HGF-induced B16F10 cell invasion (IC50 = 9 nM). |
| Animal Protocol |
Animal/Disease Models: Female mice bearing MBA-MB-231 tumors (5 per group) [1] Doses: 0, 100 mg/kg Route of Administration: Orally, once Experimental Results:Inhibition of MET and VEGFR2 phosphorylation. Animal/Disease Models: MBA-MB-231 tumor-bearing mice [1] Doses: 1, 3, 10, 30, 60 mg/kg Route of Administration: Orally, one time/day for 14 days Experimental Results: Inhibited in a dose-dependent manner Tumor growth. |
| References |
[1]. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther, 2011, 10(12), 2298-2308. [2]. VEGF and c-Met blockade amplify angiogenesis inhibition in pancreatic islet cancer. Cancer Res, 2011, 71(14), 4758-4768. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8588 mL | 9.2942 mL | 18.5884 mL | |
| 5 mM | 0.3718 mL | 1.8588 mL | 3.7177 mL | |
| 10 mM | 0.1859 mL | 0.9294 mL | 1.8588 mL |