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	640.57	26.46	192	6313	19906	50578713
Malignant neoplasm progression	547.51	26.46	234	6271	67890	50530729
Diarrhoea	263.03	26.46	347	6158	588129	50010490
Decreased appetite	162.73	26.46	162	6343	200761	50397858
Stomatitis	113.34	26.46	98	6407	101246	50497373
Hypertension	96.86	26.46	127	6378	211076	50387543
Hypothyroidism	96.36	26.46	58	6447	34067	50564552
Hepatic function abnormal	96.06	26.46	57	6448	32624	50565995
Off label use	94.05	26.46	195	6310	474231	50124388
Hair colour changes	86.40	26.46	26	6479	2698	50595921
Taste disorder	77.88	26.46	32	6473	8292	50590327
Mucosal inflammation	71.16	26.46	51	6454	40091	50558528
Fatigue	71.15	26.46	225	6280	707376	49891243
Drug ineffective	52.66	26.46	20	6485	819313	49779306
Nausea	45.06	26.46	194	6311	705204	49893415
Oral pain	44.79	26.46	32	6473	25001	50573618
Proteinuria	43.71	26.46	27	6478	16570	50582049
Hyperthyroidism	43.13	26.46	24	6481	12151	50586468
Blood thyroid stimulating hormone increased	42.40	26.46	19	6486	6073	50592546
Inappropriate schedule of product administration	40.47	26.46	48	6457	71783	50526836
Dysphonia	36.24	26.46	34	6471	38858	50559761
Death	34.72	26.46	106	6399	325273	50273346
Disease progression	33.88	26.46	51	6454	95815	50502804
Drug intolerance	30.84	26.46	79	6426	219025	50379594
Asthenia	30.41	26.46	100	6405	318942	50279677
Hyperkeratosis	29.70	26.46	14	6491	5021	50593598
Embolism	28.18	26.46	15	6490	6953	50591666
Alanine aminotransferase increased	27.03	26.46	44	6461	88315	50510304

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	1494.61	21.88	477	15331	14282	29544437
Malignant neoplasm progression	1022.03	21.88	578	15230	73281	29485438
Diarrhoea	538.67	21.88	764	15044	331934	29226785
Hypothyroidism	363.67	21.88	175	15633	15731	29542988
Decreased appetite	321.69	21.88	391	15417	144951	29413768
Hepatic function abnormal	288.89	21.88	207	15601	39052	29519667
Hypertension	264.63	21.88	318	15490	116296	29442423
Stomatitis	262.33	21.88	191	15617	36922	29521797
Hair colour changes	199.86	21.88	61	15747	1550	29557169
Proteinuria	191.47	21.88	114	15694	15690	29543029
Taste disorder	181.24	21.88	75	15733	4701	29554018
Malaise	175.61	21.88	309	15499	159293	29399426
Dysphonia	168.69	21.88	113	15695	19083	29539636
Fatigue	133.78	21.88	421	15387	316400	29242319
Drug intolerance	129.57	21.88	144	15664	48235	29510484
Blister	96.25	21.88	82	15726	19824	29538895
Disease progression	92.86	21.88	161	15647	81755	29476964
Oral pain	87.07	21.88	57	15751	9250	29549469
Dysgeusia	77.63	21.88	77	15731	22597	29536122
Drug ineffective	74.27	21.88	52	15756	363118	29195601
Inappropriate schedule of product administration	66.19	21.88	99	15709	44373	29514346
Off label use	62.54	21.88	321	15487	300479	29258240
Mucosal inflammation	61.45	21.88	80	15728	31515	29527204
Immune-mediated hepatitis	61.38	21.88	25	15783	1502	29557217
Asthenia	58.09	21.88	248	15560	215002	29343717
Nausea	56.87	21.88	304	15504	288951	29269768
Skin toxicity	55.77	21.88	31	15777	3740	29554979
Liver function test increased	53.47	21.88	47	15761	11838	29546881
Drug interaction	52.48	21.88	20	15788	197365	29361354
Blood thyroid stimulating hormone increased	47.22	21.88	26	15782	3079	29555640
Product selection error	46.07	21.88	10	15798	59	29558660
Skin ulcer	45.15	21.88	53	15755	18787	29539932
Hyperthyroidism	44.77	21.88	37	15771	8571	29550148
Adrenal insufficiency	42.26	21.88	40	15768	11074	29547645
Metastases to bone	42.25	21.88	38	15770	9860	29548859
Pulmonary embolism	41.87	21.88	112	15696	76422	29482297
Weight decreased	41.49	21.88	175	15633	150730	29407989
Death	40.85	21.88	317	15491	341767	29216952
Ageusia	37.53	21.88	34	15774	8904	29549815
Skin disorder	37.08	21.88	38	15770	11580	29547139
Liver disorder	35.98	21.88	58	15750	27691	29531028
Aspartate aminotransferase increased	34.28	21.88	89	15719	59636	29499083
Osteonecrosis of jaw	33.96	21.88	43	15765	16467	29542252
Alanine aminotransferase increased	32.14	21.88	97	15711	70847	29487872
Vomiting	30.60	21.88	206	15602	212054	29346665
Hepatic encephalopathy	30.12	21.88	36	15772	12999	29545720
Dry skin	29.24	21.88	48	15760	23259	29535460
Blood pressure increased	28.04	21.88	95	15713	73708	29485011
Hypoproteinaemia	27.55	21.88	15	15793	1737	29556982
Overdose	26.99	21.88	5	15803	79814	29478905
Tumour pain	26.88	21.88	12	15796	904	29557815
Pneumothorax	26.06	21.88	37	15771	15805	29542914
Amylase increased	26.01	21.88	22	15786	5258	29553461
Glossodynia	25.87	21.88	18	15790	3225	29555494
Glossitis	25.12	21.88	12	15796	1056	29557663
Dry mouth	24.85	21.88	43	15765	21741	29536978
Acute kidney injury	23.99	21.88	68	15740	265199	29293520
Weight increased	23.49	21.88	6	15802	76661	29482058
Dehydration	21.98	21.88	120	15688	114628	29444091

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	1873.23	20.87	574	18049	28245	64451864
Malignant neoplasm progression	789.93	20.87	458	18165	112413	64367696
Diarrhoea	626.82	20.87	893	17730	721811	63758298
Hypothyroidism	429.87	20.87	217	18406	40240	64439869
Decreased appetite	415.80	20.87	456	18167	280833	64199276
Hepatic function abnormal	394.08	20.87	240	18383	64073	64416036
Hypertension	327.94	20.87	388	18235	258873	64221236
Stomatitis	260.90	20.87	231	18392	109374	64370735
Taste disorder	231.24	20.87	91	18532	9342	64470767
Proteinuria	221.42	20.87	123	18500	27600	64452509
Hair colour changes	186.46	20.87	61	18562	3666	64476443
Dysphonia	170.18	20.87	126	18497	46256	64433853
Disease progression	152.65	20.87	196	18427	141484	64338625
Fatigue	141.92	20.87	505	18118	748225	63731884
Malaise	132.04	20.87	327	18296	395920	64084189
Drug ineffective	131.62	20.87	40	18583	840207	63639902
Mucosal inflammation	119.88	20.87	117	18506	62467	64417642
Dysgeusia	92.03	20.87	89	18534	46958	64433151
Death	87.92	20.87	322	18301	482383	63997726
Hyperthyroidism	86.66	20.87	58	18565	18121	64461988
Immune-mediated hepatitis	86.44	20.87	31	18592	2458	64477651
Asthenia	77.42	20.87	285	18338	427759	64052350
Inappropriate schedule of product administration	72.80	20.87	110	18513	92176	64387933
Blood thyroid stimulating hormone increased	72.34	20.87	38	18585	7616	64472493
Oral pain	69.37	20.87	60	18563	27433	64452676
Off label use	67.72	20.87	360	18263	632446	63847663
Alanine aminotransferase increased	66.70	20.87	133	18490	138898	64341211
Aspartate aminotransferase increased	66.58	20.87	122	18501	119666	64360443
Pneumothorax	63.28	20.87	54	18569	24244	64455865
Adrenal insufficiency	62.74	20.87	52	18571	22435	64457674
Pulmonary embolism	61.97	20.87	133	18490	146223	64333886
Product selection error	58.49	20.87	13	18610	172	64479937
Nausea	58.01	20.87	406	18217	785394	63694715
Weight decreased	55.58	20.87	195	18428	285544	64194565
Drug interaction	55.08	20.87	18	18605	362065	64118044
Amylase increased	51.27	20.87	33	18590	9652	64470457
Drug hypersensitivity	50.68	20.87	5	18618	237810	64242299
Metastases to bone	48.34	20.87	43	18580	20392	64459717
Lipase increased	48.06	20.87	37	18586	14365	64465744
Ageusia	47.22	20.87	36	18587	13777	64466332
Liver function test increased	45.05	20.87	50	18573	30920	64449189
Skin toxicity	43.86	20.87	26	18597	6576	64473533
Blood bilirubin increased	41.71	20.87	66	18557	57487	64422622
Pleural effusion	41.44	20.87	104	18519	126455	64353654
Osteonecrosis of jaw	41.07	20.87	54	18569	39771	64440338
Hypersensitivity	39.65	20.87	5	18618	196447	64283662
Hepatic encephalopathy	39.58	20.87	39	18584	21027	64459082
Blister	38.24	20.87	77	18546	80890	64399219
Weight increased	37.35	20.87	8	18615	213340	64266769
Dehydration	37.09	20.87	142	18481	216621	64263488
Toxicity to various agents	36.30	20.87	31	18592	363482	64116627
Infusion related reaction	36.26	20.87	3	18620	164464	64315645
Anal abscess	35.89	20.87	24	18599	7484	64472625
Tumour pain	34.93	20.87	15	18608	1918	64478191
Transaminases increased	34.91	20.87	53	18570	44541	64435568
Liver disorder	34.35	20.87	58	18565	53293	64426816
Joint swelling	33.99	20.87	10	18613	215372	64264737
Vomiting	33.84	20.87	273	18350	550844	63929265
Rheumatoid arthritis	33.60	20.87	4	18619	164290	64315819
Hypocalcaemia	33.22	20.87	50	18573	41703	64438406
Pain	33.09	20.87	69	18554	553442	63926667
Skin ulcer	31.27	20.87	50	18573	43924	64436185
Constipation	31.18	20.87	140	18483	229197	64250912
Nasopharyngitis	31.12	20.87	9	18614	196064	64284045
Dry skin	29.52	20.87	53	18570	51108	64429001
Colitis	29.14	20.87	57	18566	58617	64421492
Hyperkeratosis	28.71	20.87	20	18603	6661	64473448
Blood pressure increased	28.65	20.87	112	18511	172440	64307669
Skin disorder	27.72	20.87	37	18586	27643	64452466
Fall	26.57	20.87	50	18573	416776	64063333
Intestinal perforation	26.29	20.87	27	18596	15286	64464823
General physical health deterioration	25.71	20.87	122	18501	204303	64275806
Urticaria	24.82	20.87	6	18617	147311	64332798
Glossitis	24.79	20.87	14	18609	3233	64476876
Cell death	24.44	20.87	15	18608	4039	64476070
Hypoproteinaemia	24.26	20.87	14	18609	3368	64476741
Product dose omission issue	24.24	20.87	13	18610	194734	64285375
Cholecystitis	24.02	20.87	29	18594	19607	64460502
Bradycardia	23.87	20.87	3	18620	118216	64361893
Depression	23.16	20.87	12	18611	183279	64296830
Large intestine perforation	23.06	20.87	23	18600	12581	64467528
Performance status decreased	22.92	20.87	16	18607	5348	64474761
Microangiopathic haemolytic anaemia	22.76	20.87	10	18613	1352	64478757
Overdose	22.41	20.87	9	18614	159557	64320552
Injection site pain	22.07	20.87	3	18620	111405	64368704
Embolism	21.78	20.87	22	18601	12213	64467896
Pneumonitis	21.54	20.87	46	18577	50319	64429790
Scrotal dermatitis	21.45	20.87	3	18620	0	64480109
Cancer pain	21.29	20.87	14	18609	4243	64475866
Swelling	20.98	20.87	10	18613	160208	64319901

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 (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
EQ 20MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11141413	April 17, 2037	TREATMENT OF ADVANCED RENAL CELL CARCINOMA (RCC) IN PATIENTS WHO HAVE RECEIVED PRIOR ANTI-ANGIOGENIC THERAPY
EQ 40MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11141413	April 17, 2037	TREATMENT OF ADVANCED RENAL CELL CARCINOMA (RCC) IN PATIENTS WHO HAVE RECEIVED PRIOR ANTI-ANGIOGENIC THERAPY
EQ 60MG BASE	CABOMETYX	EXELIXIS INC	N208692	April 25, 2016	RX	TABLET	ORAL	11141413	April 17, 2037	TREATMENT OF ADVANCED RENAL CELL CARCINOMA (RCC) IN PATIENTS WHO HAVE RECEIVED PRIOR ANTI-ANGIOGENIC THERAPY

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. 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 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	42388-024	TABLET	20 mg	ORAL	NDA	27 sections
CABOMETYX	HUMAN PRESCRIPTION DRUG LABEL	1	42388-025	TABLET	40 mg	ORAL	NDA	27 sections