cabozantinib 🐶 Veterinary Use | 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 cabometyx	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: 4.44 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
cabometyx

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: 4.44
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:

Dose	Unit	Route
60	mg	O

ADMET properties:

None

Approvals:

Date	Agency	Company
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
Palmar-plantar erythrodysaesthesia syndrome	899.15	25.15	265	9018	22750	63456989
Malignant neoplasm progression	688.52	25.15	302	8981	81819	63397920
Diarrhoea	335.93	25.15	462	8821	714904	62764835
Hepatic function abnormal	214.94	25.15	106	9177	37036	63442703
Decreased appetite	205.27	25.15	216	9067	250836	63228903
Hypothyroidism	170.44	25.15	95	9188	42537	63437202
Taste disorder	160.09	25.15	64	9219	13598	63466141
Hypertension	139.52	25.15	187	9096	279116	63200623
Stomatitis	134.31	25.15	131	9152	138594	63341145
Hair colour changes	121.71	25.15	36	9247	3091	63476648
Off label use	106.30	25.15	274	9009	674188	62805551
Inappropriate schedule of product administration	89.16	25.15	92	9191	103873	63375866
Mucosal inflammation	83.72	25.15	63	9220	46865	63432874
Proteinuria	82.87	25.15	45	9238	19100	63460639
Blood thyroid stimulating hormone increased	71.62	25.15	30	9253	7164	63472575
Hyperthyroidism	70.57	25.15	37	9246	14636	63465103
Fatigue	68.62	25.15	283	9000	887745	62591994
Drug ineffective	66.94	25.15	35	9248	1044730	62435009
Disease progression	65.38	25.15	85	9198	122673	63357066
Nausea	57.24	25.15	261	9022	854210	62625529
Oral pain	50.35	25.15	38	9245	28356	63451383
Blood pressure increased	43.68	25.15	82	9201	161980	63317759
Alanine aminotransferase increased	40.57	25.15	62	9221	103708	63376031
Dysphonia	40.51	25.15	42	9241	47572	63432167
Hyperkeratosis	37.23	25.15	18	9265	6000	63473739
Aspartate aminotransferase increased	36.79	25.15	55	9228	90222	63389517
Dysgeusia	35.84	25.15	39	9244	46671	63433068
Weight decreased	34.84	25.15	104	9179	276694	63203045
Drug hypersensitivity	34.37	25.15	3	9280	310684	63169055
Death	34.06	25.15	126	9157	374255	63105484
Asthenia	33.98	25.15	128	9155	383476	63096263
Pneumothorax	33.89	25.15	24	9259	16237	63463502
Constipation	33.67	25.15	90	9193	224853	63254886
Hypersensitivity	31.91	25.15	3	9280	292682	63187057
Pleural effusion	30.01	25.15	51	9232	93159	63386580
Malaise	29.07	25.15	129	9154	415825	63063914
Large intestine perforation	28.76	25.15	17	9266	8465	63471274
Cancer pain	27.39	25.15	12	9271	3193	63476546
Metastases to lung	26.99	25.15	19	9264	12731	63467008
Fall	26.70	25.15	12	9271	392322	63087417
Immune-mediated hepatitis	25.44	25.15	9	9274	1362	63478377
Adrenal insufficiency	25.35	25.15	21	9262	17894	63461845
Liver disorder	25.21	25.15	35	9248	53652	63426087

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
Palmar-plantar erythrodysaesthesia syndrome	2324.70	20.55	723	22192	16072	34917944
Malignant neoplasm progression	1210.67	20.55	738	22177	87308	34846708
Diarrhoea	772.46	20.55	1097	21818	388815	34545201
Hypothyroidism	592.24	20.55	284	22631	20618	34913398
Hepatic function abnormal	589.94	20.55	365	22550	43998	34890018
Decreased appetite	494.72	20.55	575	22340	165817	34768199
Hypertension	421.00	20.55	481	22434	135962	34798054
Stomatitis	397.62	20.55	281	22634	42233	34891783
Taste disorder	381.88	20.55	152	22763	7003	34927013
Proteinuria	341.51	20.55	189	22726	18453	34915563
Malaise	332.46	20.55	501	22414	185324	34748692
Hair colour changes	247.01	20.55	78	22837	1799	34932217
Dysphonia	217.07	20.55	154	22761	23229	34910787
Disease progression	215.24	20.55	307	22608	107770	34826246
Inappropriate schedule of product administration	170.43	20.55	207	22708	62089	34871927
Fatigue	165.74	20.55	575	22340	370078	34563938
Blister	128.48	20.55	112	22803	22746	34911270
Liver disorder	110.90	20.55	122	22793	32875	34901141
Drug intolerance	107.87	20.55	162	22753	59408	34874608
Oral pain	102.01	20.55	72	22843	10755	34923261
Drug ineffective	95.13	20.55	96	22819	456655	34477361
Metastases to bone	93.32	20.55	71	22844	11899	34922117
Product selection error	82.97	20.55	18	22897	83	34933933
Drug interaction	82.62	20.55	23	22892	225923	34708093
Dysgeusia	78.86	20.55	92	22823	26405	34907611
Mucosal inflammation	72.69	20.55	107	22808	38515	34895501
Blood thyroid stimulating hormone increased	72.02	20.55	41	22874	4214	34929802
Skin toxicity	67.56	20.55	41	22874	4743	34929273
Adrenal insufficiency	67.42	20.55	63	22852	13984	34920032
Nausea	64.23	20.55	411	22504	339497	34594519
Weight decreased	63.60	20.55	256	22659	176045	34757971
Metastases to lung	61.26	20.55	50	22865	9270	34924746
Immune-mediated hepatitis	59.31	20.55	29	22886	2186	34931830
Liver function test increased	56.24	20.55	58	22857	14507	34919509
Blood pressure increased	55.98	20.55	155	22760	87947	34846069
Hyperthyroidism	55.80	20.55	50	22865	10516	34923500
Osteonecrosis of jaw	54.70	20.55	63	22852	17826	34916190
Skin ulcer	54.53	20.55	70	22845	22146	34911870
Asthenia	53.49	20.55	308	22607	244943	34689073
Skin disorder	52.38	20.55	54	22861	13501	34920515
Pulmonary embolism	48.47	20.55	149	22766	89597	34844419
Dry skin	45.44	20.55	77	22838	31210	34902806
Metastases to central nervous system	43.67	20.55	39	22876	8166	34925850
Product use in unapproved indication	42.81	20.55	12	22903	117487	34816529
Aspartate aminotransferase increased	42.79	20.55	119	22796	67664	34866352
Febrile neutropenia	41.33	20.55	19	22896	136830	34797186
Drug hypersensitivity	41.24	20.55	3	22912	80526	34853490
Alanine aminotransferase increased	38.91	20.55	129	22786	80686	34853330
Weight increased	38.90	20.55	7	22908	93026	34840990
Off label use	36.84	20.55	428	22487	419096	34514920
Ageusia	36.15	20.55	39	22876	10269	34923747
Dry mouth	34.59	20.55	67	22848	30098	34903918
Nephrotic syndrome	33.60	20.55	32	22883	7271	34926745
Death	33.12	20.55	402	22513	397647	34536369
Adverse drug reaction	31.02	20.55	63	22852	29279	34904737
Hepatic encephalopathy	31.01	20.55	43	22872	14642	34919374
Bradycardia	30.83	20.55	6	22909	75412	34858604
Hypotension	30.65	20.55	62	22853	221587	34712429
Product use issue	30.60	20.55	3	22912	63213	34870803
Urticaria	30.08	20.55	3	22912	62374	34871642
Glossitis	29.72	20.55	15	22900	1210	34932806
Immune-mediated hepatic disorder	29.22	20.55	14	22901	1009	34933007
Pneumothorax	29.07	20.55	48	22867	19044	34914972
Metastases to liver	28.84	20.55	40	22875	13623	34920393
Overdose	28.49	20.55	12	22903	91047	34842969
Vomiting	28.44	20.55	267	22648	247354	34686662
Acute kidney injury	28.16	20.55	104	22811	304884	34629132
Blood glucose increased	27.92	20.55	5	22910	66713	34867303
Amylase increased	27.17	20.55	26	22889	5942	34928074
Hypertransaminasaemia	26.62	20.55	25	22890	5581	34928435
Pneumonia	26.56	20.55	135	22780	362492	34571524
Cardiac failure congestive	26.01	20.55	11	22904	83259	34850757
Performance status decreased	24.70	20.55	21	22894	4116	34929900
Glossodynia	24.66	20.55	20	22895	3673	34930343
Hypoproteinaemia	23.92	20.55	16	22899	2188	34931828
Pancytopenia	23.32	20.55	17	22898	95140	34838876
Neutropenia	23.27	20.55	42	22873	156736	34777280
Sensitive skin	23.06	20.55	10	22905	571	34933445
Depression	22.96	20.55	18	22897	97080	34836936
Adverse event	22.96	20.55	43	22872	18834	34915182
Product dose omission issue	22.72	20.55	27	22888	119684	34814332
Impaired healing	22.60	20.55	38	22877	15296	34918720
Multiple organ dysfunction syndrome	22.53	20.55	11	22904	76555	34857461
Tumour pain	22.50	20.55	12	22903	1085	34932931
Lipase increased	22.05	20.55	29	22886	9387	34924629
Colitis	21.59	20.55	64	22851	37686	34896330
Loss of consciousness	21.28	20.55	14	22901	82653	34851363
Bleeding varicose vein	20.87	20.55	8	22907	332	34933684
Diabetes mellitus	20.76	20.55	3	22912	46870	34887146

FDA Adverse Event Reporting System (Geriatric)

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
Palmar-plantar erythrodysaesthesia syndrome	2856.79	21.03	853	26439	32281	79684815
Malignant neoplasm progression	1027.60	21.03	616	26676	135374	79581722
Diarrhoea	898.08	21.03	1285	26007	879204	78837892
Hepatic function abnormal	809.59	21.03	426	26866	72681	79644415
Hypothyroidism	736.92	21.03	359	26933	52033	79665063
Decreased appetite	610.43	21.03	664	26628	341754	79375342
Hypertension	501.14	21.03	590	26702	330402	79386694
Taste disorder	484.90	21.03	188	27104	15635	79701461
Proteinuria	401.25	21.03	204	27088	32298	79684798
Stomatitis	350.51	21.03	334	26958	146423	79570673
Disease progression	340.44	21.03	365	26927	183997	79533099
Hair colour changes	262.71	21.03	85	27207	4147	79712949
Malaise	259.48	21.03	538	26754	489331	79227765
Dysphonia	218.31	21.03	170	27122	56702	79660394
Inappropriate schedule of product administration	186.25	21.03	229	27063	133399	79583697
Drug ineffective	155.60	21.03	89	27203	1080824	78636272
Fatigue	149.39	21.03	670	26622	929057	78788039
Mucosal inflammation	136.29	21.03	148	27144	75432	79641664
Blood thyroid stimulating hormone increased	128.71	21.03	64	27228	9644	79707452
Hyperthyroidism	123.12	21.03	83	27209	22126	79694970
Liver disorder	115.46	21.03	133	27159	72284	79644812
Dysgeusia	104.87	21.03	113	27179	57064	79660032
Metastases to bone	102.41	21.03	77	27215	24350	79692746
Adrenal insufficiency	94.04	21.03	78	27214	28409	79688687
Death	91.79	21.03	410	26882	566104	79150992
Product selection error	89.50	21.03	20	27272	226	79716870
Metastases to lung	89.18	21.03	63	27229	18100	79698996
Immune-mediated hepatitis	86.21	21.03	36	27256	3620	79713476
Weight decreased	85.98	21.03	292	27000	354906	79362190
Aspartate aminotransferase increased	85.85	21.03	163	27129	138478	79578618
Alanine aminotransferase increased	84.91	21.03	178	27114	162392	79554704
Drug hypersensitivity	79.46	21.03	6	27286	298910	79418186
Drug interaction	79.32	21.03	22	27270	415161	79301935
Oral pain	78.81	21.03	74	27218	31724	79685372
Asthenia	77.37	21.03	363	26929	511326	79205770
Blood pressure increased	72.99	21.03	197	27095	211163	79505933
Pulmonary embolism	72.84	21.03	173	27119	171481	79545615
Pneumothorax	72.28	21.03	67	27225	28256	79688840
Nausea	68.85	21.03	560	26732	956636	78760460
Osteonecrosis of jaw	68.21	21.03	79	27213	43147	79673949
Pain	62.69	21.03	90	27202	703712	79013384
Weight increased	60.36	21.03	11	27281	277375	79439721
Product use issue	59.37	21.03	3	27289	209819	79507277
Skin toxicity	58.23	21.03	36	27256	8278	79708818
Joint swelling	57.57	21.03	14	27278	288632	79428464
Toxicity to various agents	55.78	21.03	38	27254	421502	79295594
Hypersensitivity	55.77	21.03	11	27281	262228	79454868
Ascites	54.56	21.03	95	27197	75467	79641629
Liver function test increased	53.45	21.03	67	27225	39706	79677390
Nasopharyngitis	53.26	21.03	11	27281	253870	79463226
Amylase increased	53.00	21.03	38	27254	11171	79705925
Dry skin	49.76	21.03	86	27206	67909	79649187
Pleural effusion	49.71	21.03	135	27157	145127	79571969
Metastases to central nervous system	48.22	21.03	42	27250	16333	79700763
Off label use	46.99	21.03	495	26797	906720	78810376
Infusion related reaction	46.22	21.03	11	27281	230226	79486870
Arthropathy	45.80	21.03	4	27288	177107	79539989
Constipation	44.26	21.03	203	27089	282847	79434249
Rheumatoid arthritis	43.79	21.03	9	27283	208461	79508635
Hepatic encephalopathy	42.96	21.03	47	27245	24119	79692977
Swelling	42.25	21.03	11	27281	216700	79500396
Lipase increased	42.10	21.03	39	27253	16427	79700669
Immune-mediated hepatic disorder	42.02	21.03	17	27275	1577	79715519
Dehydration	41.81	21.03	182	27110	248005	79469091
Ageusia	41.77	21.03	39	27253	16593	79700503
Blood bilirubin increased	41.11	21.03	78	27214	66154	79650942
Skin disorder	40.62	21.03	54	27238	33889	79683207
Product use in unapproved indication	39.68	21.03	18	27274	250341	79466755
Metastases to liver	38.52	21.03	48	27244	28266	79688830
Hyperkeratosis	38.19	21.03	27	27265	7763	79709333
Hypertransaminasaemia	38.00	21.03	32	27260	11892	79705204
Nephrotic syndrome	37.71	21.03	31	27261	11143	79705953
Skin ulcer	37.68	21.03	67	27225	54083	79663013
Cancer pain	37.46	21.03	23	27269	5222	79711874
Blister	36.90	21.03	107	27185	119369	79597727
Performance status decreased	36.66	21.03	24	27268	6089	79711007
Anal abscess	35.93	21.03	28	27264	9327	79707769
Hypocalcaemia	35.03	21.03	62	27230	49862	79667234
Urticaria	34.97	21.03	10	27282	185191	79531905
Colitis	34.49	21.03	77	27215	73230	79643866
Immune-mediated enterocolitis	34.04	21.03	21	27271	4809	79712287
Fall	33.69	21.03	73	27219	487556	79229540
Injection site pain	33.38	21.03	3	27289	129835	79587261
Sinusitis	32.66	21.03	13	27279	195488	79521608
Glossitis	30.91	21.03	18	27274	3712	79713384
Depression	30.76	21.03	18	27274	216772	79500324
Large intestine perforation	30.65	21.03	31	27261	14536	79702560
Headache	30.45	21.03	118	27174	653654	79063442
Musculoskeletal stiffness	30.30	21.03	11	27281	174997	79542099
Immune-mediated lung disease	30.06	21.03	15	27277	2275	79714821
Tumour pain	30.01	21.03	15	27277	2284	79714812
Transaminases increased	29.75	21.03	59	27233	51684	79665412
Arthralgia	27.40	21.03	102	27190	571701	79145395
Discomfort	27.26	21.03	5	27287	125612	79591484
Cell death	27.09	21.03	18	27274	4681	79712415
Vomiting	26.64	21.03	346	26946	665482	79051614
Insomnia	26.35	21.03	27	27265	245143	79471953
Condition aggravated	26.28	21.03	86	27206	501038	79216058
Oxygen saturation decreased	26.22	21.03	6	27286	129041	79588055
Bradycardia	26.18	21.03	7	27285	135550	79581546
Alpha 1 foetoprotein increased	26.16	21.03	10	27282	798	79716298
Interstitial lung disease	25.78	21.03	91	27201	112509	79604587
Anal fistula	24.98	21.03	20	27272	6924	79710172
Bleeding varicose vein	24.96	21.03	9	27283	610	79716486
Embolism	24.51	21.03	27	27265	13955	79703141
Infection	24.45	21.03	28	27264	241684	79475412
Pneumonitis	24.34	21.03	60	27232	60800	79656296
Febrile neutropenia	24.20	21.03	26	27266	230973	79486123
Anxiety	23.85	21.03	30	27262	248482	79468614
Product dose omission issue	23.63	21.03	30	27262	247507	79469589
Intestinal perforation	22.84	21.03	29	27263	17397	79699699
Gastrointestinal perforation	22.77	21.03	18	27274	6119	79710977
Dermatitis acneiform	22.38	21.03	22	27270	9971	79707125
Mobility decreased	22.33	21.03	7	27285	122168	79594928
Platelet count decreased	22.27	21.03	128	27164	194536	79522560
Hypoproteinaemia	22.13	21.03	15	27277	4031	79713065
Tumour haemorrhage	21.80	21.03	15	27277	4129	79712967
Dry mouth	21.77	21.03	73	27219	87946	79629150
Overdose	21.29	21.03	19	27273	184187	79532909
Hypoalbuminaemia	21.18	21.03	31	27261	21266	79695830

FDA Adverse Event Reporting System (Pediatric)

None

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	antineoplastic agents
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitors
CHEBI has role	CHEBI:50266	Prodrugs

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Liver cell carcinoma	indication	109841003	DOID:684
Medullary thyroid carcinoma	indication	255032005	DOID:3973
Renal cell carcinoma	indication	702391001	DOID:4450
Metastatic renal cell carcinoma	indication	702392008

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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	11098015	Jan. 15, 2030	METHOD OF TREATING MEDULLARY THYROID CANCER
EQ 80MG BASE	COMETRIQ	EXELIXIS	N203756	Nov. 29, 2012	RX	CAPSULE	ORAL	11098015	Jan. 15, 2030	METHOD OF TREATING MEDULLARY THYROID CANCER
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	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	11098015	Jan. 15, 2030	TREATMENT OF RENAL CELL CARCINOMA
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	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	11098015	Jan. 15, 2030	TREATMENT OF RENAL CELL CARCINOMA
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF ADVANCED RENAL CELL CARCINOMA
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11098015	Jan. 15, 2030	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	11098015	Jan. 15, 2030	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	8877776	Oct. 8, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	8877776	Oct. 8, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	8877776	Oct. 8, 2030	TREATMENT OF DIFFERENTIATED THYROID CANCER THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY
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	Jan. 22, 2024	FOR THE TREATMENT OF PATIENTS WITH ADVANCED RENAL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINATION 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 RENAL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINATION 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 RENAL CELL CARCINOMA, AS A FIRST-LINE TREATMENT IN COMBINATION WITH NIVOLUMAB
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2024	TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2024	TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2024	TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE
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
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2028	THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2028	THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	Sept. 17, 2028	THE TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER WITH LOCALLY ADVANCED OR METASTATIC DIFFERENTIATED THYROID CANCER (DTC) THAT HAS PROGRESSED FOLLOWING PRIOR VEGFR-TARGETED THERAPY AND WHO ARE RADIOACTIVE IODINE-REFRACTORY OR INELIGIBLE

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN	INHIBITOR	IC50	8.34	WOMBAT-PK	DRUG LABEL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN	INHIBITOR	IC50	7.95	WOMBAT-PK	DRUG LABEL
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
Angiopoietin-1 receptor	Kinase	Q02763	TIE2_HUMAN	INHIBITOR	IC50	7.85	WOMBAT-PK	DRUG LABEL
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN	INHIBITOR	IC50	8.89	WOMBAT-PK	DRUG LABEL
Ephrin type-A receptor 2	Kinase	P29317	EPHA2_HUMAN		Kd	6.13	CHEMBL
Vascular endothelial growth factor receptor 1	Kinase	P17948	VGFR1_HUMAN		IC50	7.92	CHEMBL
Vascular endothelial growth factor receptor 3	Kinase	P35916	VGFR3_HUMAN		IC50	8.22	CHEMBL
Tyrosine-protein kinase HCK	Kinase	P08631	HCK_HUMAN		Kd	5.96	CHEMBL
High affinity nerve growth factor receptor	Kinase	P04629	NTRK1_HUMAN		Kd	5.39	CHEMBL
Tyrosine-protein kinase Lyn	Kinase	P07948	LYN_HUMAN		Kd	5.88	CHEMBL
Fibroblast growth factor receptor 1	Kinase	P11362	FGFR1_HUMAN		IC50	7.95	CHEMBL
Abelson tyrosine-protein kinase 2	Kinase	P42684	ABL2_HUMAN		Kd	6.04	CHEMBL
Aurora kinase A	Kinase	O14965	AURKA_HUMAN		Kd	5.47	CHEMBL
Macrophage-stimulating protein receptor	Kinase	Q04912	RON_HUMAN	INHIBITOR	IC50	6.91	WOMBAT-PK
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	6.12	CHEMBL
Epithelial discoidin domain-containing receptor 1	Kinase	Q08345	DDR1_HUMAN		Kd	6.68	CHEMBL
Protein-tyrosine kinase 6	Kinase	Q13882	PTK6_HUMAN		Kd	5.75	CHEMBL
Tyrosine-protein kinase receptor UFO	Kinase	P30530	UFO_HUMAN		IC50	8.47	CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		Kd	6.30	CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma	Kinase	Q8TBX8	PI42C_HUMAN		Kd	5.54	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	5.62	CHEMBL
Ferrochelatase, mitochondrial	Enzyme	P22830	HEMH_HUMAN		Kd	5.58	CHEMBL
Receptor-interacting serine/threonine-protein kinase 3	Kinase	Q9Y572	RIPK3_HUMAN		Kd	5.61	CHEMBL
Tyrosine-protein kinase FRK	Kinase	P42685	FRK_HUMAN		Kd	6.25	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		Kd	5.96	CHEMBL
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN		IC50	6.65	CHEMBL
Breakpoint cluster region protein	Kinase	P11274	BCR_HUMAN		Kd	6.47	CHEMBL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	6.75	CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	5.98	CHEMBL

External reference:

ID	Source
1C39JW444G	UNII
D10062	KEGG_DRUG
4032025	VUID
N0000186139	NUI
1140909-48-3	SECONDARY_CAS_RN
4032025	VANDF
C3181682	UMLSCUI
CHEBI:72319	CHEBI
CHEMBL2105717	ChEMBL_ID
25102847	PUBCHEM_CID
DB08875	DRUGBANK_ID
CHEMBL2103868	ChEMBL_ID
9297	INN_ID
C558660	MESH_SUPPLEMENTAL_RECORD_UI
5887	IUPHAR_LIGAND_ID
1363267	RXNORM
194795	MMSL
240294	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	42388-023	TABLET	60 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	42388-024	TABLET	20 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
CABOMETYX	HUMAN PRESCRIPTION DRUG LABEL	1	42388-025	TABLET	40 mg	ORAL	NDA	27 sections
CABOMETYX	HUMAN PRESCRIPTION DRUG LABEL	1	42388-025	TABLET	40 mg	ORAL	NDA	27 sections