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
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

Molecule

Description

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:

Date	Agency	Company	Orphan
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	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 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	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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
Medullary thyroid carcinoma	indication	255032005	DOID:3973
Renal cell carcinoma	indication	702391001	DOID:4450

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)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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 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	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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN	INHIBITOR	IC50	8.28	WOMBAT-PK	DRUG LABEL
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN	INHIBITOR	IC50	10.46	WOMBAT-PK	DRUG LABEL
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN	INHIBITOR	IC50	8.89	WOMBAT-PK	DRUG LABEL
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN	INHIBITOR	IC50	8.34	WOMBAT-PK	DRUG LABEL
Angiopoietin-1 receptor	Kinase	Q02763	TIE2_HUMAN	INHIBITOR	IC50	7.84	WOMBAT-PK	DRUG LABEL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN	INHIBITOR	IC50	7.95	WOMBAT-PK	DRUG LABEL
Macrophage-stimulating protein receptor	Kinase	Q04912	RON_HUMAN	INHIBITOR	IC50	6.91	WOMBAT-PK

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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