cabozantinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4715 849217-68-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • cabozantinib malate
  • cabozantinib (S)-malate
  • cabozantinib
  • cometriq
  • XL184
  • cabozantinib S-malate
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.
  • Molecular weight: 501.51
  • Formula: C28H24FN3O5
  • CLOGP: 4.94
  • LIPINSKI: 1
  • HAC: 8
  • HDO: 2
  • TPSA: 98.78
  • ALOGS: -5.40
  • ROTB: 8

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
March 21, 2014 EMA TMC Pharma Services Ltd
Nov. 29, 2012 FDA EXELIXIS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 519.04 46.21 120 768 12008 2345189
Diarrhoea 428.56 46.21 158 730 83406 2273791
Fatigue 285.40 46.21 119 769 84754 2272443
Palmar-plantar erythrodysaesthesia syndrome 273.62 46.21 59 829 4142 2353055
Off label use 259.64 46.21 107 781 73491 2283706
Stomatitis 172.49 46.21 48 840 9662 2347535
Decreased appetite 172.35 46.21 62 826 28829 2328368
Nausea 172.06 46.21 92 796 112097 2245100
Hypertension 116.53 46.21 46 842 27315 2329882
Death 99.76 46.21 58 830 81410 2275787
Asthenia 98.70 46.21 48 840 46878 2310319
Constipation 97.72 46.21 38 850 21591 2335606
Mucosal inflammation 84.18 46.21 24 864 5200 2351997
Vomiting 82.25 46.21 49 839 71553 2285644
Dehydration 72.58 46.21 31 857 22264 2334933
Weight decreased 71.64 46.21 33 855 28338 2328859
Dysphonia 70.96 46.21 22 866 6342 2350855
Dysphagia 70.35 46.21 26 862 12779 2344418
Blister 69.62 46.21 22 866 6749 2350448
Pleural effusion 68.94 46.21 25 863 11643 2345554
Urinary tract infection 66.87 46.21 32 856 29910 2327287
Oral pain 65.62 46.21 18 870 3379 2353818
Hair colour changes 64.65 46.21 12 876 380 2356817
Pulmonary embolism 55.03 46.21 24 864 18059 2339138
Dyspnoea 53.75 46.21 39 849 78694 2278503
Pain in extremity 48.29 46.21 29 859 42511 2314686
Hyponatraemia 48.19 46.21 20 868 13305 2343892

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 893.51 47.57 250 1779 13908 1730844
Diarrhoea 622.96 47.57 267 1762 53585 1691167
Palmar-plantar erythrodysaesthesia syndrome 514.12 47.57 122 1907 3385 1741367
Fatigue 400.63 47.57 194 1835 50587 1694165
Off label use 370.14 47.57 169 1860 38402 1706350
Stomatitis 299.37 47.57 87 1942 5317 1739435
Decreased appetite 260.87 47.57 115 1914 23756 1720996
Nausea 216.57 47.57 130 1899 51066 1693686
Death 212.74 47.57 157 1872 87286 1657466
Asthenia 194.39 47.57 106 1923 34564 1710188
Hypertension 190.60 47.57 87 1942 19361 1725391
Vomiting 187.18 47.57 107 1922 38208 1706544
Dysphonia 169.23 47.57 51 1978 3504 1741248
Pulmonary embolism 168.59 47.57 71 1958 12988 1731764
Blister 141.54 47.57 46 1983 4046 1740706
Hair colour changes 133.42 47.57 28 2001 424 1744328
Dehydration 118.27 47.57 61 1968 17597 1727155
Hypothyroidism 114.34 47.57 35 1994 2525 1742227
Weight decreased 111.78 47.57 64 1965 22689 1722063
Dysgeusia 101.92 47.57 38 1991 5011 1739741
Mucosal inflammation 97.58 47.57 35 1994 4134 1740618
Oral pain 96.77 47.57 27 2002 1403 1743349
General physical health deterioration 81.07 47.57 43 1986 13075 1731677
Proteinuria 78.48 47.57 27 2002 2817 1741935
Drug intolerance 78.11 47.57 33 1996 6029 1738723
Dyspnoea 77.81 47.57 71 1958 51988 1692764
Liver function test increased 77.09 47.57 23 2006 1516 1743236
Constipation 75.67 47.57 43 1986 14957 1729795
Sepsis 72.81 47.57 46 1983 19392 1725360
Pain in extremity 72.41 47.57 45 1984 18427 1726325
Skin ulcer 71.25 47.57 25 2004 2763 1741989
Pleural effusion 70.26 47.57 37 1992 11073 1733679
Pneumothorax 64.29 47.57 23 2006 2689 1742063
Confusional state 64.20 47.57 44 1985 21234 1723518
Anaemia 64.16 47.57 50 1979 29407 1715345
Pneumonia 63.14 47.57 60 1969 46122 1698630
Pyrexia 59.11 47.57 58 1971 46342 1698410
Ageusia 55.57 47.57 18 2011 1556 1743196
Abdominal pain 52.28 47.57 39 1990 21451 1723301
Blood pressure increased 51.95 47.57 30 1999 10723 1734029
Blood bilirubin increased 51.90 47.57 25 2004 6185 1738567
Alanine aminotransferase increased 50.82 47.57 31 1998 12247 1732505
Dysphagia 50.80 47.57 29 2000 10139 1734613
Dry skin 50.43 47.57 21 2008 3691 1741061
Hypocalcaemia 50.22 47.57 20 2009 3136 1741616
Deep vein thrombosis 48.78 47.57 28 2001 9892 1734860
Rash 48.53 47.57 48 1981 38645 1706107
Thrombocytopenia 48.22 47.57 37 1992 21212 1723540

Pharmacologic Action:

SourceCodeDescription
ATC L01XE26 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Protein kinase inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50266 prodrug
FDA EPC N0000175605 Kinase Inhibitor
FDA MoA N0000175076 Protein Kinase Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Medullary thyroid carcinoma indication 255032005 DOID:3973
Renal cell carcinoma indication 702391001 DOID:4450

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.15 acidic
pKa2 11.76 acidic
pKa3 4.95 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 TREATMENT OF RENAL CELL CARCINOMA
EQ 40MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 40MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 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 8497284 Sept. 24, 2024 TREATMENT OF RENAL CELL CARCINOMA
EQ 60MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 60MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 8497284 Sept. 24, 2024 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 8497284 Sept. 24, 2024 TREATMENT OF RENAL CELL CARCINOMA
EQ 20MG BASE COMETRIQ EXELIXIS N203756 Nov. 29, 2012 RX CAPSULE ORAL 8877776 Oct. 8, 2030 METHOD OF TREATING MEDULLARY THYROID CANCER
EQ 80MG BASE COMETRIQ EXELIXIS N203756 Nov. 29, 2012 RX CAPSULE ORAL 8877776 Oct. 8, 2030 METHOD OF TREATING MEDULLARY THYROID CANCER
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 10034873 July 18, 2031 TREATMENT OF PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC) WHO HAVE BEEN PREVIOUSLY TREATED WITH SORAFENIB
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 10039757 July 18, 2031 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 40MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 10034873 July 18, 2031 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 10039757 July 18, 2031 TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 60MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL 10034873 July 18, 2031 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 10039757 July 18, 2031 TREATMENT OF ADVANCED RENAL CELL CARCINOMA

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 20MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL Dec. 19, 2020 FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
EQ 40MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL Dec. 19, 2020 FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
EQ 60MG BASE CABOMETYX EXELIXIS INC N208692 April 25, 2016 RX TABLET ORAL Dec. 19, 2020 FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA
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. 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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Proto-oncogene tyrosine-protein kinase receptor Ret Kinase INHIBITOR IC50 8.28 WOMBAT-PK DRUG LABEL
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
Mast/stem cell growth factor receptor Kit Kinase INHIBITOR IC50 8.34 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
Macrophage-stimulating protein receptor Kinase INHIBITOR IC50 6.91 WOMBAT-PK

External reference:

IDSource
D10062 KEGG_DRUG
4032025 VUID
N0000186139 NUI
C3181682 UMLSCUI
1C39JW444G UNII
9297 INN_ID
1140909-48-3 SECONDARY_CAS_RN
DB08875 DRUGBANK_ID
CHEBI:72319 CHEBI
5887 IUPHAR_LIGAND_ID
CHEMBL2103868 ChEMBL_ID
CHEMBL2105717 ChEMBL_ID
25102847 PUBCHEM_CID
C558660 MESH_SUPPLEMENTAL_RECORD_UI
763605009 SNOMEDCT_US
1363268 RXNORM
28993 MMSL
d07931 MMSL
014768 NDDF
4032025 VANDF
718844003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
COMETRIQ HUMAN PRESCRIPTION DRUG LABEL 2 42388-011 KIT 20 mg None NDA 18 sections
COMETRIQ HUMAN PRESCRIPTION DRUG LABEL 2 42388-011 KIT 80 mg None NDA 18 sections
COMETRIQ HUMAN PRESCRIPTION DRUG LABEL 2 42388-012 KIT 80 mg None NDA 18 sections
COMETRIQ HUMAN PRESCRIPTION DRUG LABEL 2 42388-012 KIT 20 mg None NDA 18 sections
COMETRIQ HUMAN PRESCRIPTION DRUG LABEL 1 42388-013 CAPSULE 20 mg ORAL NDA 18 sections
CABOMETYX HUMAN PRESCRIPTION DRUG LABEL 1 42388-023 TABLET 60 mg ORAL NDA 18 sections
CABOMETYX HUMAN PRESCRIPTION DRUG LABEL 1 42388-024 TABLET 20 mg ORAL NDA 18 sections
CABOMETYX HUMAN PRESCRIPTION DRUG LABEL 1 42388-025 TABLET 40 mg ORAL NDA 18 sections