Identification
- Summary
Cabozantinib is a tyrosine kinase inhibitor used to treat advanced renal cell carcinoma, hepatocellular carcinoma, and medullary thyroid cancer.
- Brand Names
- Cabometyx, Cometriq
- Generic Name
- Cabozantinib
- DrugBank Accession Number
- DB08875
- Background
Cabozantinib was first approved in 2012 and is a non-specific tyrosine kinase inhibitor. It was initially approved in the US under the brand name Cometriq, which is indicated for the treatment of metastatic medullary thyroid cancer.6 In 2016, a capsule formulation (Cabometyx) was approved for the treatment of advanced renal cell carcinoma, and this same formulation gained additional approval in both the US and Canada in 2019 for the treatment of hepatocellular carcinoma in previously treated patients.7,8
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Cabozantinib (DB08875)
- Weight
- Average: 501.514
Monoisotopic: 501.169999048 - Chemical Formula
- C28H24FN3O5
- Synonyms
- Cabozantinib
- External IDs
- BMS 907351
- BMS907351
- XL 184
- XL-184
- XL184
Pharmacology
- Indication
Cabozantinib is indicated for the treatment of progressive, metastatic medullary thyroid cancer.6 It is also indicated for the treatment of advanced renal cell carcinoma and for hepatocellular carcinoma in patients previously treated with sorafenib.7,8
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Advanced renal cell carcinoma Regimen in combination with: Nivolumab (DB09035) •••••••••••• •••••••• •••••• Treatment of Advanced renal cell carcinoma •••••••••••• •••••• Treatment of Advanced renal cell carcinoma •••••••••••• ••••• •••• •• •••••••••••• ••••• ••••••••• ••••• •••••• Treatment of Advanced renal cell carcinoma •••••••••••• •••••••••• ••••••• •••• ••••••••• •••••• Treatment of Hepatocellular carcinoma •••••••••••• •••••••••• ••••••• •••• ••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Cabozantinib suppresses metastasis, angiogenesis, and oncognesis by inhibiting receptor tyrosine kinases.
- Mechanism of action
Cabozantinib inhibits specific receptor tyrosine kinases such as VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, RET, MET, and TIE-2.
Target Actions Organism AHepatocyte growth factor receptor antagonistHumans AVascular endothelial growth factor receptor 2 antagonistHumans AProto-oncogene tyrosine-protein kinase receptor Ret antagonistHumans - Absorption
After oral administration, peak plasma concentration was achieved in 2-5 hours.
- Volume of distribution
The volume of distribution is 349L.
- Protein binding
Cabozantinib has extensive plasma protein binding (≥ 99.7%).
- Metabolism
Cabozantinib is metabolized mostly by CYP3A4 and, to a minor extent, by CYP2C9. Both enzyme produce an N-oxide metabolite.
- Route of elimination
Cabozantinib is eliminated mostly by the feces (54%) and also by the urine (27%).
- Half-life
Cabozantinib has a long half-life of 55 hours.
- Clearance
At steady state, the clearance is 4.4 L/hr.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Cabozantinib carries a warning of serious gastrointestinal fistulas and perforations, and potentially fatal hemoptysis and gastrointestinal hemorrhage.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Cabozantinib can be increased when it is combined with Abametapir. Abatacept The metabolism of Cabozantinib can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Cabozantinib. Acenocoumarol The metabolism of Cabozantinib can be decreased when combined with Acenocoumarol. Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Cabozantinib. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase levels of cabozantinib.
- Avoid St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of cabozantinib.
- Take on an empty stomach. Separate the administration of cabozantinib from food by at least 1 hour before or 2 hours after eating.
- Take with a full glass of water.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Cabozantinib malate DR7ST46X58 1140909-48-3 HFCFMRYTXDINDK-WNQIDUERSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cabometyx Tablet, film coated 40 mg Oral Ipsen Pharma 2020-12-16 Not applicable EU 
Cabometyx Tablet 20 mg Oral Ipsen Biopharmaceuticals Canada Inc 2018-10-10 Not applicable Canada 
Cabometyx Tablet 60 mg/1 Oral Exelixis, Inc. 2016-04-25 Not applicable US 
Cabometyx Tablet, film coated 20 mg Oral Ipsen Pharma 2020-12-16 Not applicable EU Cabometyx Tablet 60 mg Oral Ipsen Biopharmaceuticals Canada Inc 2018-10-10 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image COMETRIQ Cabozantinib malate (20 MG) + Cabozantinib malate (80 MG) Capsule Oral Ipsen Pharma 2016-05-06 Not applicable Italy 
COMETRIQ Cabozantinib malate (20 MG) + Cabozantinib malate (80 MG) Capsule Oral Ipsen Pharma 2014-10-06 Not applicable Italy Cometriq Cabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1) Capsule; Kit Oral Exelixis, Inc. 2012-11-29 Not applicable US Cometriq Cabozantinib malate (80 mg/1) + Cabozantinib malate (20 mg/1) Kit Oral Catalent Pharma Solutions, Llc 2012-11-29 2018-01-19 US COMETRIQ Cabozantinib malate (20 MG) + Cabozantinib malate (80 MG) Capsule Oral Ipsen Pharma 2016-05-06 Not applicable Italy
Categories
- ATC Codes
- L01EX07 — Cabozantinib
- Drug Categories
- Amides
- Amines
- Aniline Compounds
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Kinase Inhibitor
- Narrow Therapeutic Index Drugs
- Protein Kinase Inhibitors
- Receptor Protein-Tyrosine Kinases, antagonists & inhibitors
- Tyrosine Kinase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Ethers
- Direct Parent
- Diarylethers
- Alternative Parents
- Quinolines and derivatives / Anilides / Phenoxy compounds / Anisoles / N-arylamides / Alkyl aryl ethers / Fluorobenzenes / Pyridines and derivatives / Aryl fluorides / Cyclopropanecarboxylic acids and derivatives show 8 more
- Substituents
- Alkyl aryl ether / Anilide / Anisole / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group show 21 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organofluorine compound, dicarboxylic acid diamide, aromatic ether, quinolines (CHEBI:72317)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 1C39JW444G
- CAS number
- 849217-68-1
- InChI Key
- ONIQOQHATWINJY-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- N'1-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
- SMILES
- COC1=CC2=C(C=C1OC)C(OC1=CC=C(NC(=O)C3(CC3)C(=O)NC3=CC=C(F)C=C3)C=C1)=CC=N2
References
- General References
- Durante C, Russo D, Verrienti A, Filetti S: XL184 (cabozantinib) for medullary thyroid carcinoma. Expert Opin Investig Drugs. 2011 Mar;20(3):407-413. doi: 10.1517/13543784.2011.559163. [Article]
- Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Geczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ: Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1814-23. doi: 10.1056/NEJMoa1510016. Epub 2015 Sep 25. [Article]
- Krajewska J, Olczyk T, Jarzab B: Cabozantinib for the treatment of progressive metastatic medullary thyroid cancer. Expert Rev Clin Pharmacol. 2016;9(1):69-79. doi: 10.1586/17512433.2016.1102052. Epub 2015 Nov 4. [Article]
- Grullich C: Cabozantinib: a MET, RET, and VEGFR2 tyrosine kinase inhibitor. Recent Results Cancer Res. 2014;201:207-14. doi: 10.1007/978-3-642-54490-3_12. [Article]
- Escudier B, Lougheed JC, Albiges L: Cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2016 Dec;17(18):2499-2504. doi: 10.1080/14656566.2016.1258059. Epub 2016 Nov 22. [Article]
- FDA Approved Drug Products: Cometriq (cabozantinib) oral capsules [Link]
- FDA Approved Drug Products: Cabometyx (cabozantinib) oral tablets [Link]
- Health Canada Product Monograph: Cabometyx (cabozantinib) oral tablets [Link]
- External Links
- KEGG Drug
- D10062
- PubChem Compound
- 25102847
- PubChem Substance
- 347827806
- ChemSpider
- 25948202
- BindingDB
- 50021574
- 1363268
- ChEBI
- 72317
- ChEMBL
- CHEMBL2105717
- ZINC
- ZINC000070466416
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Cabozantinib
- FDA label
- Download (194 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 25.340 mg Tablet Oral 20 mg/1 Tablet Oral 20 mg Tablet Oral 40 mg/1 Tablet Oral 40 mg Tablet Oral 60 mg Tablet Oral 60 mg/1 Tablet, film coated Oral 20 mg Tablet, film coated Oral 40 mg Tablet, film coated Oral 60 mg Capsule Oral Capsule Oral 20 MG Capsule Oral 20 mg/1 Capsule; kit Oral Kit Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8877776 No 2014-11-04 2030-10-08 US US7579473 No 2009-08-25 2024-09-24 US US8497284 No 2013-07-30 2024-09-24 US US9724342 No 2017-08-08 2033-07-09 US US9717720 No 2017-08-01 2032-02-10 US US10039757 No 2018-08-07 2031-07-18 US US10034873 No 2018-07-31 2031-07-18 US US11098015 No 2021-08-24 2030-01-15 US US11091439 No 2021-08-17 2030-01-15 US US11091440 No 2021-08-17 2030-01-15 US US11141413 No 2021-10-12 2037-04-17 US US11298349 No 2012-02-10 2032-02-10 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility COMETRIQ is practically insoluble in water. From FDA label. - Predicted Properties
Property Value Source Water Solubility 0.00199 mg/mL ALOGPS logP 4.01 ALOGPS logP 4.66 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 13.46 Chemaxon pKa (Strongest Basic) 5.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 98.78 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 136.12 m3·mol-1 Chemaxon Polarizability 51.49 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 208.07274 predictedDeepCCS 1.0 (2019) [M+H]+ 210.4683 predictedDeepCCS 1.0 (2019) [M+Na]+ 216.38084 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including...
- Gene Name
- MET
- Uniprot ID
- P08581
- Uniprot Name
- Hepatocyte growth factor receptor
- Molecular Weight
- 155540.035 Da
References
- Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [Article]
- Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Vascular endothelial growth factor-activated receptor activity
- Specific Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation of angiogenesis, vascular development, vascular permeability, and ...
- Gene Name
- KDR
- Uniprot ID
- P35968
- Uniprot Name
- Vascular endothelial growth factor receptor 2
- Molecular Weight
- 151525.555 Da
References
- Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [Article]
- Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, You A, Laird AD, Engst S, Lee L, Lesch J, Chou YC, Joly AH: Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011 Dec;10(12):2298-308. doi: 10.1158/1535-7163.MCT-11-0264. Epub 2011 Sep 16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Transmembrane receptor protein tyrosine kinase activity
- Specific Function
- Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
- Gene Name
- RET
- Uniprot ID
- P07949
- Uniprot Name
- Proto-oncogene tyrosine-protein kinase receptor Ret
- Molecular Weight
- 124317.465 Da
References
- Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R: Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Nguyen L, Holland J, Miles D, Engel C, Benrimoh N, O'Reilly T, Lacy S: Pharmacokinetic (PK) drug interaction studies of cabozantinib: Effect of CYP3A inducer rifampin and inhibitor ketoconazole on cabozantinib plasma PK and effect of cabozantinib on CYP2C8 probe substrate rosiglitazone plasma PK. J Clin Pharmacol. 2015 Sep;55(9):1012-23. doi: 10.1002/jcph.510. Epub 2015 Jun 2. [Article]
- Gerendash BS, Creel PA: Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064. doi: 10.2147/OTT.S145295. eCollection 2017. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Cabozantinib FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Escudier B, Lougheed JC, Albiges L: Cabozantinib for the treatment of renal cell carcinoma. Expert Opin Pharmacother. 2016 Dec;17(18):2499-2504. doi: 10.1080/14656566.2016.1258059. Epub 2016 Nov 22. [Article]
Drug created at May 13, 2013 00:12 / Updated at November 01, 2023 04:04