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 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 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 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 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 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA 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:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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