ponatinib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	4716	943319-70-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ponatinib iclusig AP24534 ponatinib hydrochloride ponatinib HCl	a pan-Bcr-Abl protein kinase Inhibitor Molecular weight: 532.57 Formula: C29H27F3N6O CLOGP: 6.11 LIPINSKI: 2 HAC: 7 HDO: 1 TPSA: 65.77 ALOGS: -5.26 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ponatinib
iclusig
AP24534
ponatinib hydrochloride
ponatinib HCl

a pan-Bcr-Abl protein kinase Inhibitor

Molecular weight: 532.57
Formula: C29H27F3N6O
CLOGP: 6.11
LIPINSKI: 2
HAC: 7
HDO: 1
TPSA: 65.77
ALOGS: -5.26
ROTB: 7

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
45	mg	O

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Dec. 14, 2012	FDA	ARIAD

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
Acute lymphocytic leukaemia recurrent	215.16	22.15	49	5724	1926	50597425
Philadelphia chromosome positive	172.95	22.15	31	5742	348	50599003
Chronic myeloid leukaemia recurrent	120.96	22.15	21	5752	193	50599158
Blast crisis in myelogenous leukaemia	114.55	22.15	23	5750	489	50598862
Cytogenetic analysis abnormal	105.92	22.15	23	5750	723	50598628
Neoplasm progression	97.27	22.15	53	5720	29104	50570247
Dry skin	92.67	22.15	59	5714	43132	50556219
Drug resistance	78.93	22.15	40	5733	18949	50580402
Rash	77.38	22.15	160	5613	437311	50162040
Death	73.37	22.15	132	5641	325247	50274104
Peripheral arterial occlusive disease	70.44	22.15	23	5750	3514	50595837
Blast cell crisis	66.79	22.15	11	5762	71	50599280
Therapeutic response delayed	61.51	22.15	14	5759	547	50598804
Stem cell transplant	55.12	22.15	16	5757	1652	50597699
Thrombocytopenia	54.72	22.15	70	5703	127603	50471748
Cytopenia	50.14	22.15	23	5750	8752	50590599
Hypertension	46.58	22.15	85	5688	211118	50388233
Pleural effusion	41.90	22.15	49	5724	81405	50517946
Leukaemia recurrent	41.31	22.15	12	5761	1242	50598109
Off label use	41.25	22.15	133	5640	474293	50125058
Platelet count decreased	41.21	22.15	54	5719	100672	50498679
Graft versus host disease	41.09	22.15	18	5755	6148	50593203
Catabolic state	41.07	22.15	7	5766	57	50599294
Ichthyosis acquired	38.05	22.15	5	5768	3	50599348
Lipase increased	35.49	22.15	18	5755	8523	50590828
Pyrexia	34.27	22.15	108	5665	380095	50219256
Pancytopenia	32.74	22.15	44	5729	83986	50515365
Product administered to patient of inappropriate age	32.58	22.15	12	5761	2618	50596733
Chemotherapy	31.76	22.15	10	5763	1359	50597992
Chronic myeloid leukaemia transformation	30.93	22.15	6	5767	106	50599245
Central nervous system leukaemia	30.46	22.15	6	5767	115	50599236
Soft tissue necrosis	28.23	22.15	7	5766	396	50598955
Ischaemic stroke	27.42	22.15	19	5754	15929	50583422
Peripheral artery stenosis	26.34	22.15	7	5766	522	50598829
Philadelphia positive acute lymphocytic leukaemia	26.09	22.15	4	5769	15	50599336
Pancreatitis	25.93	22.15	28	5745	42586	50556765
Capillary leak syndrome	24.81	22.15	9	5764	1881	50597470
Skin exfoliation	23.89	22.15	24	5749	33588	50565763
Bone pain	23.58	22.15	28	5745	47201	50552150
Skin wrinkling	22.79	22.15	7	5766	876	50598475
Graft versus host disease in skin	22.17	22.15	9	5764	2547	50596804

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
Acute lymphocytic leukaemia recurrent	227.90	21.34	63	7357	2453	29564654
Drug resistance	200.75	21.34	101	7319	21439	29545668
Neoplasm progression	181.45	21.34	90	7330	18522	29548585
Cytogenetic analysis abnormal	152.24	21.34	34	7386	536	29566571
Blast crisis in myelogenous leukaemia	126.34	21.34	29	7391	520	29566587
Chronic myeloid leukaemia recurrent	114.60	21.34	22	7398	155	29566952
Loss of therapeutic response	90.10	21.34	20	7400	306	29566801
Philadelphia chromosome positive	79.53	21.34	18	7402	302	29566805
Blast cell crisis	68.69	21.34	13	7407	84	29567023
Lipase increased	65.77	21.34	35	7385	8302	29558805
Autoimmune lymphoproliferative syndrome	61.72	21.34	13	7407	153	29566954
Drug intolerance	61.53	21.34	68	7352	48311	29518796
Death	60.29	21.34	205	7215	341879	29225228
Blast cells present	57.17	21.34	15	7405	476	29566631
Peripheral arterial occlusive disease	47.78	21.34	24	7396	5052	29562055
Viral haemorrhagic cystitis	47.54	21.34	15	7405	925	29566182
Pleural effusion	47.29	21.34	73	7347	71835	29495272
Chronic myeloid leukaemia transformation	45.61	21.34	10	7410	144	29566963
Hepatotoxicity	43.55	21.34	36	7384	17831	29549276
Gallbladder oedema	42.86	21.34	10	7410	193	29566914
Pancreatitis	41.26	21.34	47	7373	34467	29532640
Stem cell transplant	40.01	21.34	16	7404	1971	29565136
Loss of CAR T-cell persistence	39.78	21.34	7	7413	28	29567079
Cytokine release syndrome	39.64	21.34	30	7390	13089	29554018
Central nervous system neoplasm	39.54	21.34	8	7412	76	29567031
Bone marrow transplant	39.37	21.34	13	7407	927	29566180
Haematopoietic stem cell mobilisation	39.06	21.34	9	7411	164	29566943
Platelet count decreased	38.99	21.34	83	7337	104589	29462518
Renal artery stenosis	36.77	21.34	15	7405	1946	29565161
Thrombocytopenia	36.15	21.34	94	7326	134729	29432378
Clonal evolution	35.93	21.34	8	7412	124	29566983
Graft versus host disease	35.87	21.34	25	7395	9603	29557504
Cytopenia	35.34	21.34	25	7395	9834	29557273
Central nervous system leukaemia	35.24	21.34	9	7411	256	29566851
Hepatic calcification	32.92	21.34	9	7411	335	29566772
Adrenomegaly	32.59	21.34	9	7411	348	29566759
Acute lymphocytic leukaemia	32.53	21.34	15	7405	2616	29564491
Metamyelocyte count increased	31.89	21.34	9	7411	377	29566730
Renal artery stent placement	30.97	21.34	5	7415	10	29567097
Renal artery angioplasty	30.97	21.34	5	7415	10	29567097
Costal cartilage fracture	30.76	21.34	8	7412	245	29566862
Transplant	30.64	21.34	10	7410	687	29566420
Periarthritis calcarea	29.85	21.34	6	7414	55	29567052
Post transplant lymphoproliferative disorder	29.65	21.34	18	7402	5475	29561632
Articular calcification	29.56	21.34	6	7414	58	29567049
Graft versus host disease in gastrointestinal tract	29.48	21.34	15	7405	3243	29563864
Dry skin	28.29	21.34	32	7388	23275	29543832
Immature granulocyte count increased	28.00	21.34	6	7414	77	29567030
Myelocyte count increased	27.90	21.34	8	7412	355	29566752
Adrenal cyst	27.65	21.34	6	7414	82	29567025
Bone pain	27.06	21.34	28	7392	18424	29548683
Red cell distribution width increased	26.90	21.34	16	7404	4691	29562416
Epstein-Barr virus infection	26.55	21.34	18	7402	6611	29560496
Off label use	26.15	21.34	146	7274	300654	29266453
Hypertension	25.96	21.34	76	7344	116538	29450569
Gastrointestinal wall thickening	25.60	21.34	10	7410	1158	29565949
Bone neoplasm	25.41	21.34	7	7413	268	29566839
Treatment failure	24.94	21.34	38	7382	36901	29530206
Peripheral vascular disorder	24.74	21.34	15	7405	4552	29562555
Diaphragmatic disorder	23.64	21.34	9	7411	973	29566134
Graft versus host disease in skin	23.35	21.34	13	7407	3366	29563741
Monocyte count decreased	22.66	21.34	9	7411	1089	29566018
Activated partial thromboplastin time prolonged	21.84	21.34	17	7403	7725	29559382

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
Acute lymphocytic leukaemia recurrent	321.20	20.16	83	10242	3943	64484464
Drug resistance	196.84	20.16	101	10224	35001	64453406
Philadelphia chromosome positive	182.42	20.16	37	10288	580	64487827
Blast crisis in myelogenous leukaemia	172.43	20.16	37	10288	772	64487635
Neoplasm progression	160.56	20.16	93	10232	40871	64447536
Cytogenetic analysis abnormal	122.54	20.16	29	10296	952	64487455
Chronic myeloid leukaemia recurrent	120.12	20.16	23	10302	263	64488144
Peripheral arterial occlusive disease	97.16	20.16	38	10287	6949	64481458
Lipase increased	85.20	20.16	43	10282	14359	64474048
Platelet count decreased	83.95	20.16	118	10207	167593	64320814
Pleural effusion	80.22	20.16	100	10225	126459	64361948
Dry skin	75.92	20.16	64	10261	51097	64437310
Blast cell crisis	75.38	20.16	14	10311	134	64488273
Stem cell transplant	70.68	20.16	25	10300	3456	64484951
Thrombocytopenia	68.68	20.16	126	10199	223675	64264732
Autoimmune lymphoproliferative syndrome	66.14	20.16	13	10312	172	64488235
Death	64.40	20.16	196	10129	482509	64005898
Rash	60.02	20.16	185	10140	458364	64030043
Hypertension	59.17	20.16	129	10196	259132	64229275
Cytopenia	57.59	20.16	34	10291	15437	64472970
Renal artery stenosis	55.29	20.16	20	10305	2949	64485458
Loss of therapeutic response	54.84	20.16	12	10313	275	64488132
Cytokine release syndrome	50.67	20.16	35	10290	20794	64467613
Therapeutic response delayed	50.50	20.16	14	10311	868	64487539
Graft versus host disease	50.48	20.16	30	10295	13783	64474624
Bone marrow transplant	49.53	20.16	15	10310	1272	64487135
Central nervous system leukaemia	46.10	20.16	11	10314	374	64488033
Viral haemorrhagic cystitis	46	20.16	15	10310	1620	64486787
Off label use	44.97	20.16	210	10115	632596	63855811
Product administered to patient of inappropriate age	43.51	20.16	19	10306	4582	64483825
Neutrophil count decreased	42.60	20.16	57	10268	77139	64411268
Peripheral artery stenosis	41.90	20.16	13	10312	1196	64487211
Adrenomegaly	41.11	20.16	10	10315	369	64488038
Haematopoietic stem cell mobilisation	41.09	20.16	9	10316	207	64488200
Clonal evolution	40.61	20.16	9	10316	219	64488188
Chronic myeloid leukaemia transformation	40.08	20.16	9	10316	233	64488174
Loss of CAR T-cell persistence	36.79	20.16	6	10319	24	64488383
Hepatic calcification	36.42	20.16	9	10316	355	64488052
Hepatotoxicity	36.15	20.16	38	10287	39924	64448483
Central nervous system neoplasm	35.58	20.16	7	10318	93	64488314
Catabolic state	35.58	20.16	7	10318	93	64488314
Costal cartilage fracture	34.27	20.16	8	10317	247	64488160
Renal artery angioplasty	33.21	20.16	5	10320	10	64488397
Ichthyosis acquired	33.21	20.16	5	10320	10	64488397
Blast cells present	33.16	20.16	10	10315	836	64487571
Amylase increased	32.71	20.16	20	10305	9665	64478742
Periarthritis calcarea	32.54	20.16	6	10319	55	64488352
Philadelphia positive acute lymphocytic leukaemia	32.16	20.16	6	10319	59	64488348
Metamyelocyte count increased	31.54	20.16	9	10316	620	64487787
Pancytopenia	31.14	20.16	70	10255	143239	64345168
Hepatic function abnormal	30.26	20.16	44	10281	64269	64424138
Adrenal cyst	30.01	20.16	6	10319	87	64488320
Articular calcification	29.58	20.16	6	10319	94	64488313
Renal artery stent placement	29.27	20.16	5	10320	28	64488379
Skin exfoliation	29.24	20.16	36	10289	44849	64443558
Pyrexia	28.95	20.16	170	10155	558474	63929933
Leukaemia recurrent	28.79	20.16	12	10313	2582	64485825
Acute lymphocytic leukaemia	28.65	20.16	14	10311	4357	64484050
Carotid artery stenosis	28.37	20.16	17	10308	7924	64480483
Pancreatitis	28.36	20.16	41	10284	59566	64428841
Chronic graft versus host disease	26.57	20.16	15	10310	6261	64482146
Neutropenia	26.11	20.16	91	10234	239533	64248874
Liver disorder	25.83	20.16	37	10288	53314	64435093
Epstein-Barr virus infection	25.80	20.16	19	10306	12469	64475938
Myelocyte count increased	25.70	20.16	8	10317	744	64487663
Post transplant lymphoproliferative disorder	25.50	20.16	17	10308	9527	64478880
Cerebral infarction	25.26	20.16	32	10293	41012	64447395
Abdominal pain	24.56	20.16	107	10218	312268	64176139
Malignant neoplasm progression	24.36	20.16	55	10270	112816	64375591
Diaphragmatic disorder	24.29	20.16	9	10316	1419	64486988
Red cell distribution width increased	23.80	20.16	18	10307	12291	64476116
Febrile neutropenia	23.76	20.16	75	10250	187582	64300825
Activated partial thromboplastin time prolonged	23.14	20.16	18	10307	12813	64475594
Bone pain	23.04	20.16	33	10292	47539	64440868
Fall	22.74	20.16	20	10305	416806	64071601
Chronic myeloid leukaemia	22.70	20.16	11	10314	3363	64485044
Ichthyosis	22.32	20.16	5	10320	128	64488279
Soft tissue necrosis	22.18	20.16	7	10318	681	64487726
Peripheral vascular disorder	22.01	20.16	14	10311	7247	64481160
Blast cell count increased	21.53	20.16	8	10317	1271	64487136
Activated partial thromboplastin time shortened	21.27	20.16	7	10318	778	64487629
Drug hypersensitivity	21.03	20.16	6	10319	237809	64250598
Carotid arteriosclerosis	21.01	20.16	9	10316	2070	64486337
Blood bilirubin increased	20.96	20.16	35	10290	57518	64430889
White blood cell count decreased	20.82	20.16	64	10261	157773	64330634
Coronary artery stenosis	20.76	20.16	16	10309	11232	64477175
Graft versus host disease in skin	20.55	20.16	12	10313	5335	64483072
Transplant	20.50	20.16	7	10318	871	64487536

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EA05	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS BCR-ABL tyrosine kinase inhibitors
FDA MoA	N0000175076	Protein Kinase Inhibitors
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chronic myeloid leukemia	indication	92818009	DOID:8552
Philadelphia chromosome-positive acute lymphoblastic leukemia	indication	425688002

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.98	acidic
pKa2	8.49	Basic
pKa3	5.58	Basic
pKa4	4.36	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 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR THE TREATMENT OF LEUKEMIAS
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD OF TREATING CHRONIC MYELOGENOUS LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR THE TREATMENT OF LEUKEMIAS
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD OF TREATING CHRONIC MYELOGENOUS LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR THE TREATMENT OF LEUKEMIAS
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD OF TREATING CHRONIC MYELOGENOUS LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR THE TREATMENT OF LEUKEMIAS
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9029533	Dec. 22, 2026	A METHOD OF TREATING CHRONIC MYELOGENOUS LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192895	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING LEUKEMIA RESULTING FROM A MUTATION IN THE BCR-ABL KINASE DOMAIN
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	11192897	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING CHRONIC MYELOID LEUKEMIA
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	9493470	Dec. 12, 2033	A METHOD FOR TREATING PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 10MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 18, 2020	RX	TABLET	ORAL	Dec. 18, 2023	CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINASE INHIBITORS
EQ 15MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	Dec. 18, 2023	CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINASE INHIBITORS
EQ 30MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	April 23, 2015	RX	TABLET	ORAL	Dec. 18, 2023	CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINASE INHIBITORS
EQ 45MG BASE	ICLUSIG	TAKEDA PHARMS USA	N203469	Dec. 14, 2012	RX	TABLET	ORAL	Dec. 18, 2023	CHRONIC PHASE (CP) CHRONIC MYELOID LEUKEMIA (CML) WITH RESISTANCE OR INTOLERANCE TO AT LEAST TWO PRIOR KINASE INHIBITORS

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Breakpoint cluster region protein	Kinase	P11274	BCR_HUMAN	INHIBITOR	Kd	7.30	CHEMBL	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN	INHIBITOR	IC50	9.43	WOMBAT-PK	CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN		IC50	7.59	CHEMBL
Vascular endothelial growth factor receptor 1	Kinase	P17948	VGFR1_HUMAN		IC50	8.43	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	6.11	CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN		IC50	8.92	CHEMBL
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN	INHIBITOR	IC50	7.90	WOMBAT-PK
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	8.52	CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	7.62	CHEMBL
Tyrosine-protein kinase Yes	Kinase	P07947	YES_HUMAN		Kd	6.66	CHEMBL
Tyrosine-protein kinase Fyn	Kinase	P06241	FYN_HUMAN		Kd	7.44	CHEMBL
Ephrin type-A receptor 2	Kinase	P29317	EPHA2_HUMAN		Kd	7.57	CHEMBL
Serine/threonine-protein kinase B-raf	Kinase	P15056	BRAF_HUMAN		Kd	5.92	CHEMBL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN		IC50	9.52	CHEMBL
Myosin light chain kinase, smooth muscle	Kinase	Q15746	MYLK_HUMAN		Kd	7	CHEMBL
Fibroblast growth factor receptor 3	Kinase	P22607	FGFR3_HUMAN		IC50	8.03	CHEMBL
Tyrosine-protein kinase HCK	Kinase	P08631	HCK_HUMAN		Kd	7.09	CHEMBL
Tyrosine-protein kinase JAK1	Kinase	P23458	JAK1_HUMAN		IC50	7.49	CHEMBL
Tyrosine-protein kinase JAK2	Kinase	O60674	JAK2_HUMAN		IC50	6.77	CHEMBL
Tyrosine-protein kinase CSK	Kinase	P41240	CSK_HUMAN	INHIBITOR	IC50	8.27	WOMBAT-PK
Tyrosine-protein kinase Lyn	Kinase	P07948	LYN_HUMAN	INHIBITOR	IC50	9.62	WOMBAT-PK
Fibroblast growth factor receptor 1	Kinase	P11362	FGFR1_HUMAN	INHIBITOR	IC50	8.66	WOMBAT-PK
Abelson tyrosine-protein kinase 2	Kinase	P42684	ABL2_HUMAN		Kd	7.70	CHEMBL
Mitogen-activated protein kinase 11	Kinase	Q15759	MK11_HUMAN		Kd	6	CHEMBL
Ephrin type-A receptor 5	Kinase	P54756	EPHA5_HUMAN		Kd	8.10	CHEMBL
Ephrin type-A receptor 4	Kinase	P54764	EPHA4_HUMAN		Kd	4.77	CHEMBL
Fibroblast growth factor receptor 2	Kinase	P21802	FGFR2_HUMAN		IC50	8.89	CHEMBL
TRAF2 and NCK-interacting protein kinase	Kinase	Q9UKE5	TNIK_HUMAN		Kd	6.42	CHEMBL
Tyrosine-protein kinase Fgr	Kinase	P09769	FGR_HUMAN		Kd	7.42	CHEMBL
Mitogen-activated protein kinase 14	Kinase	Q16539	MK14_HUMAN		Kd	6.81	CHEMBL
Tyrosine-protein kinase FRK	Kinase	P42685	FRK_HUMAN		Kd	7.03	CHEMBL
Cyclin-G-associated kinase	Kinase	O14976	GAK_HUMAN		Kd	5.73	CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		IC50	8.17	CHEMBL
Cyclin-dependent kinase 16	Kinase	Q00536	CDK16_HUMAN		Kd	5.76	CHEMBL
Mitogen-activated protein kinase 9	Kinase	P45984	MK09_HUMAN		Kd	5.10	CHEMBL
Calcium/calmodulin-dependent protein kinase kinase 2	Kinase	Q96RR4	KKCC2_HUMAN		Kd	5.75	CHEMBL
Epithelial discoidin domain-containing receptor 1	Kinase	Q08345	DDR1_HUMAN		Kd	7.75	CHEMBL
Ephrin type-B receptor 4	Kinase	P54760	EPHB4_HUMAN		Kd	5.83	CHEMBL
TGF-beta receptor type-2	Kinase	P37173	TGFR2_HUMAN		Kd	5.75	CHEMBL
MAP kinase-activated protein kinase 2	Kinase	P49137	MAPK2_HUMAN		Kd	6.33	CHEMBL
Tyrosine-protein kinase BTK	Kinase	Q06187	BTK_HUMAN		Kd	5.74	CHEMBL
Ephrin type-B receptor 2	Kinase	P29323	EPHB2_HUMAN		Kd	5.73	CHEMBL
Non-receptor tyrosine-protein kinase TNK1	Kinase	Q13470	TNK1_HUMAN		Kd	7.08	CHEMBL
Cyclin-dependent kinase 17	Kinase	Q00537	CDK17_HUMAN		Kd	6.47	CHEMBL
Mitogen-activated protein kinase kinase kinase MLT	Kinase	Q9NYL2	MLTK_HUMAN		Kd	7.39	CHEMBL
Protein-tyrosine kinase 2-beta	Kinase	Q14289	FAK2_HUMAN		Kd	6.53	CHEMBL
Maternal embryonic leucine zipper kinase	Kinase	Q14680	MELK_HUMAN		Kd	5.53	CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		Kd	7.06	CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1	Kinase	Q92918	M4K1_HUMAN		Kd	6.11	CHEMBL
cAMP-dependent protein kinase catalytic subunit alpha	Kinase	P17612	KAPCA_HUMAN		IC50	6.21	CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 4	Kinase	O95819	M4K4_HUMAN		Kd	6.51	CHEMBL
Cyclin-dependent kinase 19	Kinase	Q9BWU1	CDK19_HUMAN	INHIBITOR	Kd	7.92	IUPHAR
Cyclin-dependent kinase 8	Kinase	P49336	CDK8_HUMAN	INHIBITOR	Kd	8.17	IUPHAR
Ephrin type-A receptor 1	Kinase	P21709	EPHA1_HUMAN		Kd	5.94	CHEMBL
Ephrin type-B receptor 3	Kinase	P54753	EPHB3_HUMAN		Kd	6.26	CHEMBL
Receptor-interacting serine/threonine-protein kinase 1	Kinase	Q13546	RIPK1_HUMAN	INHIBITOR	IC50	7.92	IUPHAR
Fibroblast growth factor receptor 4	Kinase	P22455	FGFR4_HUMAN		IC50	8.15	CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 2	Kinase	Q12851	M4K2_HUMAN		Kd	7.39	CHEMBL
Interleukin-1 receptor-associated kinase 4	Kinase	Q9NWZ3	IRAK4_HUMAN		Kd	5.66	CHEMBL
Interleukin-1 receptor-associated kinase 1	Kinase	P51617	IRAK1_HUMAN		Kd	6.16	CHEMBL
Serine/threonine-protein kinase TAO3	Kinase	Q9H2K8	TAOK3_HUMAN		Kd	5.67	CHEMBL
Serine/threonine-protein kinase ULK3	Kinase	Q6PHR2	ULK3_HUMAN		Kd	5.76	CHEMBL
Mitogen-activated protein kinase kinase kinase 1	Kinase	Q13233	M3K1_HUMAN		Kd	6.31	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	5.53	CHEMBL
Bcr/Abl fusion protein	Kinase	P00519 P11274	ABL1_HUMAN BCR_HUMAN		IC50	9.30	CHEMBL
Receptor-interacting serine/threonine-protein kinase 3	Kinase	Q9Y572	RIPK3_HUMAN	INHIBITOR	Ki	8.80	IUPHAR
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN	INHIBITOR	IC50	8.82	WOMBAT-PK
ATP-dependent RNA helicase DDX1	Enzyme	Q92499	DDX1_HUMAN		Kd	7.07	CHEMBL
Platelet-derived growth factor receptor alpha	Kinase	P16234	PGFRA_HUMAN	INHIBITOR	IC50	8.96	WOMBAT-PK
Proto-oncogene tyrosine-protein kinase Src	Kinase		SRC_CHICK		IC50	9.05	CHEMBL

External reference:

ID	Source
4340891KFS	UNII
D09950	KEGG_DRUG
4032031	VUID
N0000186141	NUI
1114544-31-8	SECONDARY_CAS_RN
4032031	VANDF
C2987417	UMLSCUI
CHEBI:78543	CHEBI
0LI	PDB_CHEM_ID
CHEMBL1171837	ChEMBL_ID
24826799	PUBCHEM_CID
DB08901	DRUGBANK_ID
CHEMBL2105708	ChEMBL_ID
9362	INN_ID
C545373	MESH_SUPPLEMENTAL_RECORD_UI
5890	IUPHAR_LIGAND_ID
1364347	RXNORM
196462	MMSL
29016	MMSL
31534	MMSL
d07936	MMSL
014797	NDDF
014798	NDDF
703796003	SNOMEDCT_US
703797007	SNOMEDCT_US
703798002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-533	TABLET, FILM COATED	30 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-533	TABLET, FILM COATED	30 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-534	TABLET, FILM COATED	45 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-534	TABLET, FILM COATED	45 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-535	TABLET, FILM COATED	15 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-535	TABLET, FILM COATED	15 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-536	TABLET, FILM COATED	10 mg	ORAL	NDA	33 sections
Iclusig	HUMAN PRESCRIPTION DRUG LABEL	1	63020-536	TABLET, FILM COATED	10 mg	ORAL	NDA	33 sections