cabozantinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |
| Stem definition | Drug id | CAS RN |
|---|---|---|
| tyrosine kinase inhibitors | 4715 | 849217-68-1 |
Description:
| Molecule | Description |
|---|---|
|
Synonyms:
|
Cabozantinib inhibits the tyrosine kinase activity of MET, VEGFR-1, -2 and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, drug resistance, and maintenance of the tumor microenvironment.
Legend: OFP - off patent OFM - off market ONP - on patent |
Drug dosage:
None
ADMET properties:
None
Approvals:
| Date | Agency | Company | Orphan |
|---|---|---|---|
| March 25, 2020 | PMDA | Takeda Pharmaceutical Company Limited | |
| March 21, 2014 | EMA | TMC Pharma Services Ltd | |
| Nov. 29, 2012 | FDA | EXELIXIS |
FDA Adverse Event Reporting System (Female)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Malignant neoplasm progression | 470.85 | 31.00 | 191 | 4337 | 64735 | 46616799 |
| Palmar-plantar erythrodysaesthesia syndrome | 347.16 | 31.00 | 113 | 4415 | 20338 | 46661196 |
| Diarrhoea | 179.57 | 31.00 | 243 | 4285 | 559359 | 46122175 |
| Decreased appetite | 104.06 | 31.00 | 110 | 4418 | 193726 | 46487808 |
| Stomatitis | 97.40 | 31.00 | 68 | 4460 | 68229 | 46613305 |
| Off label use | 91.82 | 31.00 | 145 | 4383 | 379696 | 46301838 |
| Hair colour changes | 70.40 | 31.00 | 19 | 4509 | 1773 | 46679761 |
| Fatigue | 64.89 | 31.00 | 165 | 4363 | 608532 | 46073002 |
| Drug intolerance | 55.97 | 31.00 | 70 | 4458 | 146979 | 46534555 |
| Hypertension | 54.28 | 31.00 | 80 | 4448 | 196276 | 46485258 |
| Mucosal inflammation | 49.03 | 31.00 | 36 | 4492 | 38940 | 46642594 |
| Hypothyroidism | 39.53 | 31.00 | 29 | 4499 | 31309 | 46650225 |
| Taste disorder | 37.95 | 31.00 | 16 | 4512 | 5862 | 46675672 |
| Drug ineffective | 37.26 | 31.00 | 10 | 4518 | 677828 | 46003706 |
| Oral pain | 35.99 | 31.00 | 25 | 4503 | 24772 | 46656762 |
| Nausea | 32.67 | 31.00 | 142 | 4386 | 687312 | 45994222 |
| Death | 32.43 | 31.00 | 88 | 4440 | 335460 | 46346074 |
| Embolism | 31.85 | 31.00 | 15 | 4513 | 7123 | 46674411 |
FDA Adverse Event Reporting System (Male)
| MedDRA adverse event term | Likelihood ratio | Likelihood ratio threshold | Patients taking drug having adverse event | Patients taking drug not having adverse event | Patients not taking drug having adverse event | Patients not taking drug not having adverse event |
|---|---|---|---|---|---|---|
| Malignant neoplasm progression | 890.18 | 23.26 | 458 | 10328 | 71829 | 29869863 |
| Palmar-plantar erythrodysaesthesia syndrome | 773.55 | 23.26 | 264 | 10522 | 14606 | 29927086 |
| Diarrhoea | 316.31 | 23.26 | 484 | 10302 | 333619 | 29608073 |
| Stomatitis | 188.41 | 23.26 | 134 | 10652 | 37145 | 29904547 |
| Hypothyroidism | 171.95 | 23.26 | 91 | 10695 | 14872 | 29926820 |
| Decreased appetite | 160.27 | 23.26 | 231 | 10555 | 149679 | 29792013 |
| Hypertension | 141.42 | 23.26 | 195 | 10591 | 121159 | 29820533 |
| Drug intolerance | 140.33 | 23.26 | 122 | 10664 | 45169 | 29896523 |
| Hair colour changes | 131.13 | 23.26 | 40 | 10746 | 1525 | 29940167 |
| Dysphonia | 126.15 | 23.26 | 81 | 10705 | 18951 | 29922741 |
| Fatigue | 111.38 | 23.26 | 308 | 10478 | 320365 | 29621327 |
| Off label use | 81.91 | 23.26 | 235 | 10551 | 249055 | 29692637 |
| Dysgeusia | 73.09 | 23.26 | 65 | 10721 | 24736 | 29916956 |
| Blister | 70.68 | 23.26 | 59 | 10727 | 20624 | 29921068 |
| Proteinuria | 65.66 | 23.26 | 51 | 10735 | 16094 | 29925598 |
| Oral pain | 59.51 | 23.26 | 39 | 10747 | 9430 | 29932262 |
| Death | 58.24 | 23.26 | 268 | 10518 | 357015 | 29584677 |
| Mucosal inflammation | 56.42 | 23.26 | 62 | 10724 | 30432 | 29911260 |
| Pulmonary embolism | 52.66 | 23.26 | 98 | 10688 | 78037 | 29863655 |
| Immune-mediated hepatitis | 50.85 | 23.26 | 18 | 10768 | 1098 | 29940594 |
| Nausea | 49.21 | 23.26 | 224 | 10562 | 296733 | 29644959 |
| Liver function test increased | 46.84 | 23.26 | 36 | 10750 | 11180 | 29930512 |
| Skin toxicity | 46.70 | 23.26 | 23 | 10763 | 3226 | 29938466 |
| Asthenia | 42.78 | 23.26 | 175 | 10611 | 221115 | 29720577 |
| Drug ineffective | 40.41 | 23.26 | 38 | 10748 | 340349 | 29601343 |
| Blood thyroid stimulating hormone increased | 40.40 | 23.26 | 20 | 10766 | 2836 | 29938856 |
| Vomiting | 40.26 | 23.26 | 171 | 10615 | 219647 | 29722045 |
| Weight decreased | 36.25 | 23.26 | 128 | 10658 | 150793 | 29790899 |
| Adrenal insufficiency | 36.04 | 23.26 | 30 | 10756 | 10433 | 29931259 |
| Skin ulcer | 36.03 | 23.26 | 39 | 10747 | 18810 | 29922882 |
| Renal cell carcinoma | 32.02 | 23.26 | 22 | 10764 | 5744 | 29935948 |
| Hypoproteinaemia | 29.56 | 23.26 | 14 | 10772 | 1802 | 29939890 |
| Hyperthyroidism | 29.52 | 23.26 | 24 | 10762 | 8074 | 29933618 |
| Ageusia | 29.45 | 23.26 | 25 | 10761 | 8928 | 29932764 |
| Tumour pain | 26.98 | 23.26 | 11 | 10775 | 989 | 29940703 |
| Hepatic encephalopathy | 26.48 | 23.26 | 29 | 10757 | 14163 | 29927529 |
| Drug interaction | 26.41 | 23.26 | 20 | 10766 | 199548 | 29742144 |
| Aspartate aminotransferase increased | 25.91 | 23.26 | 65 | 10721 | 63357 | 29878335 |
| Microangiopathic haemolytic anaemia | 25.42 | 23.26 | 10 | 10776 | 819 | 29940873 |
| Anal abscess | 25.03 | 23.26 | 18 | 10768 | 5051 | 29936641 |
| Alanine aminotransferase increased | 24.18 | 23.26 | 70 | 10716 | 74206 | 29867486 |
| General physical health deterioration | 24.15 | 23.26 | 85 | 10701 | 99859 | 29841833 |
| Taste disorder | 23.49 | 23.26 | 15 | 10771 | 3468 | 29938224 |
Pharmacologic Action:
| Source | Code | Description |
|---|---|---|
| ATC | L01EX07 | ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors |
| FDA MoA | N0000175076 | Protein Kinase Inhibitors |
| FDA EPC | N0000175605 | Kinase Inhibitor |
| CHEBI has role | CHEBI:35610 | cytostatic |
| CHEBI has role | CHEBI:38637 | tyrosine kinase inhibitors |
| CHEBI has role | CHEBI:50266 | prodrugs |
Drug Use (View source of the data)
| Disease | Relation | SNOMED_ID | DOID |
|---|---|---|---|
| Medullary thyroid carcinoma | indication | 255032005 | DOID:3973 |
| Renal cell carcinoma | indication | 702391001 | DOID:4450 |
| Metastatic renal cell carcinoma | indication | 702392008 |
Acid dissociation constants calculated using MoKa v3.0.0
| Dissociation level | Dissociation constant | Type (acidic/basic) |
|---|---|---|
| pKa1 | 11.15 | acidic |
| pKa2 | 11.76 | acidic |
| pKa3 | 4.95 | Basic |
Orange Book patent data (new drug applications)
None
Orange Book exclusivity data (new drug applications)
| Formulation strength | Trade name | Applicant | Application number | Approval date | Type | Dose form | Route | Exclusivity date | Description |
|---|---|---|---|---|---|---|---|---|---|
| EQ 20MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2022 | TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
| EQ 40MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2022 | TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
| EQ 60MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2022 | TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
| EQ 20MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 22, 2024 | FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENULLL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINULLTION WITH NIVOLUMAB |
| EQ 40MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 22, 2024 | FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENULLL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINULLTION WITH NIVOLUMAB |
| EQ 60MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 22, 2024 | FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENULLL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINULLTION WITH NIVOLUMAB |
| EQ 20MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2026 | INDICATED FOR TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
| EQ 40MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2026 | INDICATED FOR TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
| EQ 60MG BASE | CABOMETYX | EXELIXIS INC | N208692 | April 25, 2016 | RX | TABLET | ORAL | Jan. 14, 2026 | INDICATED FOR TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB |
Bioactivity Summary:
| Target | Class | Pharos | UniProt | Action | Type | Activity value (-log[M]) | Mechanism action | Bioact source | MoA source |
|---|---|---|---|---|---|---|---|---|---|
| Vascular endothelial growth factor receptor 2 | Kinase | INHIBITOR | IC50 | 10.46 | WOMBAT-PK | DRUG LABEL | |||
| Hepatocyte growth factor receptor | Kinase | INHIBITOR | IC50 | 8.89 | WOMBAT-PK | DRUG LABEL | |||
| Proto-oncogene tyrosine-protein kinase receptor Ret | Kinase | INHIBITOR | IC50 | 8.28 | WOMBAT-PK | DRUG LABEL | |||
| Angiopoietin-1 receptor | Kinase | INHIBITOR | IC50 | 7.84 | WOMBAT-PK | DRUG LABEL | |||
| Receptor-type tyrosine-protein kinase FLT3 | Kinase | INHIBITOR | IC50 | 7.95 | WOMBAT-PK | DRUG LABEL | |||
| Mast/stem cell growth factor receptor Kit | Kinase | INHIBITOR | IC50 | 8.34 | WOMBAT-PK | DRUG LABEL | |||
| Macrophage-stimulating protein receptor | Kinase | INHIBITOR | IC50 | 6.91 | WOMBAT-PK |
External reference:
| ID | Source |
|---|---|
| D10062 | KEGG_DRUG |
| 4032025 | VUID |
| N0000186139 | NUI |
| 1140909-48-3 | SECONDARY_CAS_RN |
| 4032025 | VANDF |
| C3181682 | UMLSCUI |
| CHEBI:72319 | CHEBI |
| CHEMBL2105717 | ChEMBL_ID |
| CHEMBL2103868 | ChEMBL_ID |
| DB08875 | DRUGBANK_ID |
| 9297 | INN_ID |
| C558660 | MESH_SUPPLEMENTAL_RECORD_UI |
| 25102847 | PUBCHEM_CID |
| 5887 | IUPHAR_LIGAND_ID |
| 1C39JW444G | UNII |
| 1363267 | RXNORM |
| 194795 | MMSL |
| 28993 | MMSL |
| 31609 | MMSL |
| d07931 | MMSL |
| 014768 | NDDF |
| 014782 | NDDF |
| 718844003 | SNOMEDCT_US |
| 763605009 | SNOMEDCT_US |
| 864011003 | SNOMEDCT_US |
Pharmaceutical products:
| Product | Category | Ingredients | NDC | Form | Quantity | Route | Marketing | Label |
|---|---|---|---|---|---|---|---|---|
| COMETRIQ | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42388-013 | CAPSULE | 20 mg | ORAL | NDA | 27 sections |
| CABOMETYX | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42388-023 | TABLET | 60 mg | ORAL | NDA | 27 sections |
| CABOMETYX | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42388-024 | TABLET | 20 mg | ORAL | NDA | 27 sections |
| CABOMETYX | HUMAN PRESCRIPTION DRUG LABEL | 1 | 42388-025 | TABLET | 40 mg | ORAL | NDA | 27 sections |