Details of the Drug

General Information of Drug (ID: DMIYDT4)

Drug Name

Cabozantinib

Synonyms

Cabometyx; Cometriq

Indication

Disease Entry	ICD 11	Status	REF
Medullary thyroid gland carcinoma	N.A.	Approved	[1]
Thyroid cancer	2D10	Approved	[2]
Ovarian cancer	2C73	Phase 2	[2]
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Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

501.5

Logarithm of the Partition Coefficient (xlogp)

5.4

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 2-5 h []
Half-life: The concentration or amount of drug in body reduced by one-half in 55 hours [3]
Metabolism: The drug is metabolized via the CYP3A4 and CYP2C9 []
Vd: The volume of distribution (Vd) of drug is 349 L []

Chemical Identifiers

Formula: C28H24FN3O5
IUPAC Name: 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Canonical SMILES: COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F
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)
InChIKey: ONIQOQHATWINJY-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 25102847
ChEBI ID: CHEBI:72317
CAS Number: 849217-68-1
DrugBank ID: DB08875
TTD ID: D0IQ6P
INTEDE ID: DR0254
ACDINA ID: D00087

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[4]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[6]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Protein Interaction/Cellular Processes	[7]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Post-Translational Modifications	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Medullary thyroid gland carcinoma

ICD Disease Classification

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
Proto-oncogene c-Met (MET)	DTT	MET	1.08E-03	-0.24	-0.4
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	1.90E-01	-9.81E-03	-5.96E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-01

Molecular Expression Atlas (MEA)

MEA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cabozantinib

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Lenvatinib	DMB1IU4	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Lenvatinib.	Thyroid cancer [2D10]	[9]
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Coadministration of a Drug Treating the Disease Different from Cabozantinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Metreleptin	DM1NOEK	Moderate	Increased metabolism of Cabozantinib caused by Metreleptin mediated induction of CYP450 enzyme.	Acute diabete complication [5A2Y]	[10]
Ivosidenib	DM8S6T7	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Ivosidenib.	Acute myeloid leukaemia [2A60]	[11]
Arn-509	DMT81LZ	Major	Increased metabolism of Cabozantinib caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[10]
Oliceridine	DM6MDCF	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Oliceridine.	Acute pain [MG31]	[12]
Ivabradine	DM0L594	Major	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Ivabradine.	Angina pectoris [BA40]	[9]
Bedaquiline	DM3906J	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[13]
Levalbuterol	DM5YBO1	Moderate	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Levalbuterol.	Asthma [CA23]	[14]
Pexidartinib	DMS2J0Z	Moderate	Increased metabolism of Cabozantinib caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[10]
Talazoparib	DM1KS78	Moderate	Decreased clearance of Cabozantinib due to the transporter inhibition by Talazoparib.	Breast cancer [2C60-2C6Y]	[15]
Tucatinib	DMBESUA	Major	Decreased metabolism of Cabozantinib caused by Tucatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[16]
PF-04449913	DMSB068	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and PF-04449913.	Chronic myelomonocytic leukaemia [2A40]	[9]
Olodaterol	DM62B78	Moderate	Increased risk of prolong QT interval by the combination of Cabozantinib and Olodaterol.	Chronic obstructive pulmonary disease [CA22]	[17]
Vilanterol	DMF5EK1	Moderate	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Vilanterol.	Chronic obstructive pulmonary disease [CA22]	[14]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Cabozantinib and Levomilnacipran.	Chronic pain [MG30]	[18]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Cabozantinib and Regorafenib.	Colorectal cancer [2B91]	[9]
Osilodrostat	DMIJC9X	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Osilodrostat.	Cushing syndrome [5A70]	[9]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Cabozantinib caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[10]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Cabozantinib caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[19]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Cabozantinib and Vortioxetine.	Depression [6A70-6A7Z]	[18]
Ingrezza	DMVPLNC	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Ingrezza.	Dystonic disorder [8A02]	[9]
Stiripentol	DMMSDOY	Moderate	Decreased metabolism of Cabozantinib caused by Stiripentol mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[19]
Eslicarbazepine	DMZREFQ	Moderate	Increased metabolism of Cabozantinib caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[10]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Cabozantinib caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[10]
Ripretinib	DM958QB	Moderate	Decreased clearance of Cabozantinib due to the transporter inhibition by Ripretinib.	Gastrointestinal stromal tumour [2B5B]	[16]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Cabozantinib and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[9]
Fostemsavir	DM50ILT	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Fostemsavir.	Human immunodeficiency virus disease [1C60-1C62]	[9]
Cobicistat	DM6L4H2	Major	Decreased metabolism of Cabozantinib caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[16]
Aliskiren	DM1BV7W	Moderate	Decreased clearance of Cabozantinib due to the transporter inhibition by Aliskiren.	Hypertension [BA00-BA04]	[20]
Lesinurad	DMUR64T	Moderate	Increased metabolism of Cabozantinib caused by Lesinurad mediated induction of CYP450 enzyme.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[10]
Berotralstat	DMWA2DZ	Major	Decreased clearance of Cabozantinib due to the transporter inhibition by Berotralstat.	Innate/adaptive immunodeficiency [4A00]	[21]
Polyethylene glycol	DM4I1JP	Moderate	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Polyethylene glycol.	Irritable bowel syndrome [DD91]	[9]
Naloxegol	DML0B41	Minor	Decreased clearance of Cabozantinib due to the transporter inhibition by Naloxegol.	Large intestine motility disorder [DB32]	[22]
Brigatinib	DM7W94S	Moderate	Increased metabolism of Cabozantinib caused by Brigatinib mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[10]
Ceritinib	DMB920Z	Major	Decreased metabolism of Cabozantinib caused by Ceritinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[16]
PF-06463922	DMKM7EW	Moderate	Increased metabolism of Cabozantinib caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[10]
Osimertinib	DMRJLAT	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Osimertinib.	Lung cancer [2C25]	[23]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Selpercatinib.	Lung cancer [2C25]	[9]
GDC-0199	DMH0QKA	Major	Decreased clearance of Cabozantinib due to the transporter inhibition by GDC-0199.	Mature B-cell leukaemia [2A82]	[16]
IPI-145	DMWA24P	Moderate	Decreased metabolism of Cabozantinib caused by IPI-145 mediated inhibition of CYP450 enzyme.	Mature B-cell leukaemia [2A82]	[19]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Cabozantinib and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[24]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Cabozantinib and Ibrutinib.	Mature B-cell lymphoma [2A85]	[19]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Cabozantinib and Ponatinib.	Mature B-cell lymphoma [2A85]	[25]
Arry-162	DM1P6FR	Major	Increased risk of bleeding by the combination of Cabozantinib and Arry-162.	Melanoma [2C30]	[19]
Vemurafenib	DM62UG5	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Vemurafenib.	Melanoma [2C30]	[20]
LGX818	DMNQXV8	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and LGX818.	Melanoma [2C30]	[9]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Cabozantinib caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[9]
Siponimod	DM2R86O	Major	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Siponimod.	Multiple sclerosis [8A40]	[16]
Ozanimod	DMT6AM2	Major	Increased risk of ventricular arrhythmias by the combination of Cabozantinib and Ozanimod.	Multiple sclerosis [8A40]	[26]
Fedratinib	DM4ZBK6	Moderate	Decreased metabolism of Cabozantinib caused by Fedratinib mediated inhibition of CYP450 enzyme.	Myeloproliferative neoplasm [2A20]	[19]
Ruxolitinib	DM7Q98D	Major	Increased risk of bleeding by the combination of Cabozantinib and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[19]
Vorapaxar	DMA16BR	Major	Increased risk of bleeding by the combination of Cabozantinib and Vorapaxar.	Myocardial infarction [BA41-BA43]	[19]
Entrectinib	DMMPTLH	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Entrectinib.	Non-small cell lung cancer [2C25]	[9]
Rucaparib	DM9PVX8	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Rucaparib.	Ovarian cancer [2C73]	[9]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Cabozantinib and MK-4827.	Ovarian cancer [2C73]	[9]
Triclabendazole	DMPWGBR	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Triclabendazole.	Parasitic worm infestation [1F90]	[9]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Cabozantinib caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[27]
Macimorelin	DMQYJIR	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Macimorelin.	Pituitary gland disorder [5A60-5A61]	[28]
Enzalutamide	DMGL19D	Major	Increased metabolism of Cabozantinib caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[10]
Relugolix	DMK7IWL	Major	Decreased clearance of Cabozantinib due to the transporter inhibition by Relugolix.	Prostate cancer [2C82]	[29]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Cabozantinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[19]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Cabozantinib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[16]
LEE011	DMMX75K	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and LEE011.	Solid tumour/cancer [2A00-2F9Z]	[20]
Pitolisant	DM8RFNJ	Major	Increased risk of prolong QT interval by the combination of Cabozantinib and Pitolisant.	Somnolence [MG42]	[9]
Fostamatinib	DM6AUHV	Moderate	Decreased metabolism of Cabozantinib caused by Fostamatinib mediated inhibition of CYP450 enzyme.	Thrombocytopenia [3B64]	[30]
Elagolix	DMB2C0E	Moderate	Increased metabolism of Cabozantinib caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[10]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Cabozantinib and Betrixaban.	Venous thromboembolism [BD72]	[19]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Isopropyl alcohol	E00070	3776	Antimicrobial preservative; Solvent
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Ammonia	E00007	222	Alkalizing agent
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Butyl alcohol	E00011	263	Flavoring agent; Solvent
Carmellose sodium	E00625	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Ferric oxide black	E00522	16211978	Colorant
Ferrosoferric oxide	E00231	14789	Colorant
Hydroxypropyl cellulose	E00632	Not Available	Binding agent; Coating agent; Emulsifying agent; Film/Membrane-forming agent; Modified-release agent; Suspending agent; Viscosity-controlling agent
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Propylene glycol	E00040	1030	Antimicrobial preservative; Humectant; Plasticizing agent; Solvent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
Haematite red	E00236	14833	Colorant
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Ammonium hydroxide	E00687	Not Available	Alkalizing agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
Shellac	E00695	Not Available	Coating agent; Film/membrane-forming agent; Microencapsulating agent; Modified-release agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Cabozantinib 20 mg capsule	20 mg	Oral Capsule	Oral
Cabozantinib S-Malate eq 80mg base capsule	eq 80mg base	Capsule	Oral
Cabozantinib S-Malate eq 20mg base capsule	eq 20mg base	Capsule	Oral
Cabozantinib S-Malate eq 20mg base tablet	eq 20mg base	Tablet	Oral
Cabozantinib S-Malate eq 40mg base tablet	eq 40mg base	Tablet	Oral
Cabozantinib S-Malate eq 60mg base tablet	eq 60mg base	Tablet	Oral
Cabozantinib 20 mg tablet	20 mg	Oral Tablet	Oral
Cabozantinib 40 mg tablet	40 mg	Oral Tablet	Oral
Cabozantinib 60 mg tablet	60 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Cabozantinib FDA Label
2	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5887).
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Clinical pipeline report, company report or official report of Exelixis (2011).
5	Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064.
6	FDA Label of Cabozantinib. The 2020 official website of the U.S. Food and Drug Administration.
7	Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
8	ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol. 2019 Nov 15;383:114768. doi: 10.1016/j.taap.2019.114768. Epub 2019 Oct 19.
9	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
10	Product Information. Cabometyx (cabozantinib). Exelixis Inc, S San Francisco, CA.
11	Product Information. Tibsovo (ivosidenib). Agios Pharmaceuticals, Cambridge, MA.
12	Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.
13	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
14	Product Information. Arcapta Neohaler (indacaterol). Novartis Pharmaceuticals, East Hanover, NJ.
15	Product Information. Talzenna (talazoparib). Pfizer U.S. Pharmaceuticals Group, New York, NY.
16	Cerner Multum, Inc. "Australian Product Information.".
17	Bengtsson B, Fagerstrom PO "Extrapulmonary effects of terbutaline during prolonged administration." Clin Pharmacol Ther 31 (1982): 726-32. [PMID: 7042176]
18	Alderman CP, Moritz CK, Ben-Tovim DI "Abnormal platelet aggregation associated with fluoxetine therapy." Ann Pharmacother 26 (1992): 1517-9. [PMID: 1482806]
19	Product Information. Cometriq (cabozantinib). Exelixis Inc, S San Francisco, CA.
20	Canadian Pharmacists Association.
21	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
22	Product Information. Movantik (naloxegol). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
23	Product Information. Tagrisso (osimertinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
24	Product Information. Calquence (acalabrutinib). Astra-Zeneca Pharmaceuticals, Wilmington, DE.
25	Product Information. Iclusig (ponatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
26	Product Information. Zeposia (ozanimod). Celgene Corporation, Summit, NJ.
27	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
28	Product Information. Macrilen (macimorelin). Aeterna Zentaris, Charleston, SC.
29	Product Information. Orgovyx (relugolix). Myovant Sciences, Inc., Brisbane, CA.
30	Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.