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Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	1932	641571-10-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: nilotinib hydrochloride hydrate nilotinib tasigna nilotinib hydrochloride monohydrate	Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine BCR-ABL xenograft model. Molecular weight: 529.53 Formula: C28H22F3N7O CLOGP: 5.69 LIPINSKI: 2 HAC: 8 HDO: 2 TPSA: 97.62 ALOGS: -5.42 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

nilotinib hydrochloride hydrate
nilotinib
tasigna
nilotinib hydrochloride monohydrate

Nilotinib is an inhibitor of the BCR-ABL kinase. Nilotinib binds to and stabilizes the inactive conformation of the kinase domain of ABL protein. In vitro, nilotinib inhibited BCR-ABL mediated proliferation of murine leukemic cell lines and human cell lines derived from patients with Ph+ CML. Under the conditions of the assays, nilotinib was able to overcome imatinib resistance resulting from BCR-ABL kinase mutations, in 32 out of 33 mutations tested. In vivo, nilotinib reduced the tumor size in a murine BCR-ABL xenograft model.

Molecular weight: 529.53
Formula: C28H22F3N7O
CLOGP: 5.69
LIPINSKI: 2
HAC: 8
HDO: 2
TPSA: 97.62
ALOGS: -5.42
ROTB: 7

Status: ONP

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

Drug dosage:

Dose	Unit	Route
0.60	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	4 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	21.58 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	30 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

Property	Description	Value	Unit	Confidence	Similarity
azlogd74	LogD at pH 7.4	4.722		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	3.873		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	8.110	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	14.256	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	0.660	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	1.420	%	High	1
herg	hERG pIC50	5.637	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	12.331	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	84.528	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	0.380	%	High	1
kinase-safety-class	ACVR2B,ALK,AURKA,AXL,BLK,BRAF,CAMK2B,CAMK2D,CDK5,CDK9,CSF1R,DDR1,DYRK1B,EGFR,EIF2AK3,EPHA2,EPHB4,ERBB2,FLT3,FYN,GRK2,ITK,JAK1,KIT,LCK,LYN,MAP3K21,MAP4K1,MAPK10,MAPK11,MAPK7,MAPKAPK2,MET,NTRK2,NTRK3,PDK2,PDK4,PIK3CG,PRKCD,PRKDC,SIK2,SIK3,STK33,TTK,YES1	45
kinase-selectivity-class	ABL2,ACVR2A,ALK,AURKA,AXL,BLK,BRAF,CAMK2B,CAMK2D,CDK9,CSF1R,DDR1,DYRK1B,EPHA2,EPHB4,FLT3,FYN,GRK2,JAK1,KIT,LYN,MAP3K21,MAP4K1,MAP4K3,MAPK7,MTOR,PDK4,PIK3CD,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK	34
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	11.194		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	34.754		High	1
mppb	Mouse plasma protein binding (% unbound)	0.300		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	8.630		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	1
pld-class	Phospholipidosis risk class (1 = positive, 0 = negative)	1		High	1
pppb	Pig plasma protein binding (% unbound)	1.110	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	17.338	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	3.980	%	High	1
rppb	Rat plasma protein binding (% unbound)	0.350	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	0.608	uM	High	1

Approvals:

Date	Agency	Company	Orphan
Oct. 29, 2007	FDA	NOVARTIS

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
Cytogenetic analysis abnormal	709.17	16.76	135	23289	875	90604148
Peripheral arterial occlusive disease	402.59	16.76	113	23311	4508	90600515
Electrocardiogram QT prolonged	386.82	16.76	238	23186	72218	90532805
Blast crisis in myelogenous leukaemia	327.40	16.76	66	23358	595	90604428
Drug resistance	300.44	16.76	150	23274	30299	90574724
Pleural effusion	247.83	16.76	216	23208	111775	90493248
Lipase increased	236.96	16.76	94	23330	11017	90594006
Second primary malignancy	236.08	16.76	92	23332	10286	90594737
Chronic myeloid leukaemia transformation	226.15	16.76	38	23386	103	90604920
Philadelphia chromosome positive	225.34	16.76	46	23378	444	90604579
Myocardial infarction	164.53	16.76	168	23256	105804	90499219
Bone pain	156.38	16.76	129	23295	61854	90543169
Intermittent claudication	156.13	16.76	44	23380	1779	90603244
Blood bilirubin increased	152.40	16.76	110	23314	43360	90561663
Malignant neoplasm progression	140.32	16.76	155	23269	106715	90498308
Death	138.87	16.76	340	23084	456211	90148812
Peripheral artery stenosis	137.68	16.76	32	23392	588	90604435
Rash	136.57	16.76	483	22941	795617	89809406
Off label use	124.88	16.76	65	23359	1102187	89502836
Myalgia	121.14	16.76	185	23239	174940	90430083
Acute myocardial infarction	119.35	16.76	87	23337	34803	90570220
Chronic myeloid leukaemia recurrent	119.32	16.76	25	23399	277	90604746
Thrombocytopenia	117.79	16.76	201	23223	208524	90396499
Platelet count decreased	106.64	16.76	153	23271	136816	90468207
Pancreatitis	105.24	16.76	109	23315	69717	90535306
Haematotoxicity	104.05	16.76	55	23369	12480	90592543
Carotid artery stenosis	96.12	16.76	40	23384	5294	90599729
Arteriosclerosis	94.01	16.76	49	23375	10804	90594219
Cytopenia	87.12	16.76	55	23369	17394	90587629
Cerebrovascular accident	86.07	16.76	131	23293	123402	90481621
Pancytopenia	84.45	16.76	128	23296	120135	90484888
White blood cell count increased	82.18	16.76	94	23330	67147	90537876
Peripheral vascular disorder	79.49	16.76	37	23387	6394	90598629
Joint swelling	78.76	16.76	17	23407	503283	90101740
Systemic lupus erythematosus	77.10	16.76	4	23420	361892	90243131
Platelet count increased	75.87	16.76	54	23370	20805	90584218
Pericardial effusion	75.29	16.76	68	23356	36765	90568258
Acute lymphocytic leukaemia recurrent	72.21	16.76	27	23397	2694	90602329
Splenomegaly	70.24	16.76	43	23381	12881	90592142
Myocardial ischaemia	70.11	16.76	44	23380	13770	90591253
Blast cell crisis	69.85	16.76	13	23411	73	90604950
Arthropathy	69.59	16.76	7	23417	366235	90238788
Anaemia	68.88	16.76	224	23200	352578	90252445
Glossodynia	67.16	16.76	4	23420	321775	90283248
Angina pectoris	66.07	16.76	65	23359	39095	90565928
Hyperbilirubinaemia	62.35	16.76	41	23383	13895	90591128
Condition aggravated	58.96	16.76	41	23383	595504	90009519
Coronary artery disease	58.95	16.76	57	23367	33566	90571457
Thrombocytosis	58.90	16.76	31	23393	6970	90598053
Chronic myeloid leukaemia	58.40	16.76	23	23401	2641	90602382
Rheumatoid arthritis	57.20	16.76	12	23412	362602	90242421
Gene mutation identification test positive	56.70	16.76	12	23412	140	90604883
Blood glucose increased	55.33	16.76	93	23331	95153	90509870
Palpitations	53.82	16.76	113	23311	136615	90468408
Bone marrow failure	53.46	16.76	53	23371	32168	90572855
Amylase increased	53.00	16.76	29	23395	7043	90597980
Therapeutic response delayed	52.84	16.76	16	23408	834	90604189
Diabetes mellitus	51.22	16.76	73	23351	64802	90540221
Polymerase chain reaction positive	49.73	16.76	11	23413	160	90604863
Pruritus	49.06	16.76	272	23152	541253	90063770
Exposure via father	48.66	16.76	12	23412	286	90604737
Drug hypersensitivity	47.08	16.76	31	23393	463578	90141445
Exposure via partner	47.07	16.76	10	23414	119	90604904
Wound	45.82	16.76	11	23413	302969	90302054
Lower respiratory tract infection	44.58	16.76	6	23418	250653	90354370
Musculoskeletal stiffness	44.38	16.76	11	23413	296521	90308502
Labelled drug-food interaction medication error	44.34	16.76	11	23413	269	90604754
Peripheral artery occlusion	43.65	16.76	16	23408	1510	90603513
Impaired healing	43.13	16.76	5	23419	234194	90370829
Mobility decreased	42.30	16.76	7	23417	250727	90354296
Fibromyalgia	41.73	16.76	3	23421	206266	90398757
Discomfort	41.40	16.76	10	23414	274325	90330698
Arterial disorder	41.17	16.76	15	23409	1391	90603632
Concomitant disease aggravated	40.01	16.76	29	23395	11489	90593534
Xanthelasma	39.49	16.76	8	23416	74	90604949
Drug intolerance	39.29	16.76	223	23201	447368	90157655
Intentional product use issue	39.03	16.76	5	23419	216887	90388136
Atrial fibrillation	37.80	16.76	97	23327	133514	90471509
Concomitant disease progression	37.75	16.76	16	23408	2216	90602807
Acute coronary syndrome	37.05	16.76	27	23397	10786	90594237
Leukaemia recurrent	36.91	16.76	14	23410	1453	90603570
Irritable bowel syndrome	36.81	16.76	5	23419	207443	90397580
Ill-defined disorder	36.53	16.76	3	23421	184888	90420135
Basophil count increased	36.41	16.76	13	23411	1138	90603885
Product use issue	36.36	16.76	20	23404	329899	90275124
Sinusitis	36.10	16.76	22	23402	343066	90261957
Stomatitis	36.00	16.76	13	23411	274685	90330338
Transaminases increased	35.66	16.76	46	23378	37146	90567877
Hypersensitivity	35.63	16.76	39	23385	454638	90150385
Leukocytosis	35.63	16.76	42	23382	30948	90574075
Wheezing	35.29	16.76	9	23415	238071	90366952
Pericarditis	35.04	16.76	13	23411	270138	90334885
Gamma-glutamyltransferase increased	34.92	16.76	46	23378	37906	90567117
Dry skin	34.88	16.76	73	23351	88000	90517023
Skin disorder	34.57	16.76	45	23379	36661	90568362
Peripheral ischaemia	33.75	16.76	20	23404	5647	90599376
Cardiac failure	33.60	16.76	82	23342	109414	90495609
Abdominal pain	33.30	16.76	195	23229	395526	90209497
Confusional state	32.67	16.76	31	23393	386174	90218849
Normal newborn	32.56	16.76	35	23389	23327	90581696
Alanine aminotransferase increased	32.53	16.76	85	23339	118253	90486770
Therapeutic response decreased	31.68	16.76	71	23353	89658	90515365
Haemoglobin decreased	30.78	16.76	102	23322	161854	90443169
Osteoarthritis	29.79	16.76	7	23417	195723	90409300
Folliculitis	29.76	16.76	8	23416	204345	90400678
Dyslipidaemia	29.65	16.76	23	23401	10084	90594939
Swelling	29.58	16.76	39	23385	419019	90186004
Myelofibrosis	29.07	16.76	12	23412	1555	90603468
Gene mutation	28.66	16.76	13	23411	2117	90602906
Hyperglycaemia	28.57	16.76	49	23375	50921	90554102
Nausea	28.49	16.76	423	23001	1109893	89495130
Food interaction	28.01	16.76	11	23413	1253	90603770
Psoriasis	27.58	16.76	3	23421	147751	90457272
Arterial occlusive disease	27.46	16.76	24	23400	12422	90592601
Cerebral infarction	27.24	16.76	34	23390	26562	90578461
Exposure during pregnancy	26.92	16.76	14	23410	238396	90366627
Vertebral artery hypoplasia	26.81	16.76	4	23420	3	90605020
Neoplasm malignant	26.55	16.76	38	23386	33842	90571181
Blood lactate dehydrogenase increased	26.32	16.76	33	23391	25899	90579124
Vertebral artery stenosis	26.31	16.76	6	23418	101	90604922
Skin toxicity	25.69	16.76	18	23406	6761	90598262
Pregnancy of partner	25.56	16.76	5	23419	38	90604985
Hepatic function abnormal	25.29	16.76	44	23380	46244	90558779
Haemolytic transfusion reaction	25	16.76	4	23420	7	90605016
Coronary artery stenosis	24.80	16.76	16	23408	5250	90599773
Injury	24.75	16.76	10	23414	197339	90407684
Blast cell count increased	24.69	16.76	8	23416	521	90604502
Liver injury	24.23	16.76	7	23417	170560	90434463
Cerebral artery stenosis	23.82	16.76	8	23416	583	90604440
Pain in extremity	23.70	16.76	198	23226	450331	90154692
Jaundice	23.35	16.76	35	23389	32482	90572541
Collateral circulation	22.82	16.76	4	23420	15	90605008
Ischaemic stroke	22.17	16.76	28	23396	22138	90582885
Blister	22.10	16.76	20	23404	254978	90350045
Angiopathy	21.82	16.76	15	23409	5465	90599558
Chylothorax	21.82	16.76	7	23417	442	90604581
Oncologic complication	21.67	16.76	6	23418	227	90604796
Infarction	21.60	16.76	12	23412	3001	90602022
Gangrene	21.02	16.76	21	23403	12855	90592168
Abdominal discomfort	20.94	16.76	59	23365	477269	90127754
Pancreatic enzymes increased	20.80	16.76	8	23416	862	90604161
Keratosis pilaris	20.09	16.76	5	23419	124	90604899
Fluid retention	19.98	16.76	59	23365	88032	90516991
Overdose	19.76	16.76	8	23416	157701	90447322
Cerebrovascular stenosis	19.75	16.76	4	23420	37	90604986
Aspartate aminotransferase increased	19.70	16.76	65	23359	102872	90502151
Skin sensitisation	19.60	16.76	8	23416	1007	90604016
Gastrointestinal tract irritation	19.53	16.76	7	23417	619	90604404
Hypotension	19.36	16.76	34	23390	325363	90279660
Peripheral artery thrombosis	19.20	16.76	10	23414	2200	90602823
Calculus bladder	19.16	16.76	7	23417	654	90604369
Neutropenia	18.99	16.76	111	23313	224793	90380230
Myelodysplastic syndrome	18.71	16.76	25	23399	20878	90584145
Asthma	18.69	16.76	21	23403	242139	90362884
Headache	18.41	16.76	319	23105	862427	89742596
Chest pain	18.15	16.76	143	23281	319502	90285521
Hepatotoxicity	18.15	16.76	38	23386	45804	90559219
Incorrect dose administered	18.02	16.76	53	23371	78877	90526146
Infection	17.99	16.76	42	23382	362052	90242971
Muscle spasms	17.94	16.76	119	23305	251764	90353259
Neoplasm progression	17.76	16.76	37	23387	44449	90560574
Product use in unapproved indication	17.52	16.76	38	23386	336198	90268825
Acute myeloid leukaemia	17.43	16.76	24	23400	20616	90584407
Extremity necrosis	17.42	16.76	9	23415	1948	90603075
Delirium	17.40	16.76	3	23421	104356	90500667
Capillary leak syndrome	17.10	16.76	10	23414	2757	90602266
Therapeutic product effect incomplete	17.05	16.76	15	23409	193881	90411142

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
Cytogenetic analysis abnormal	476.24	15.01	107	25315	668	42595245
Blast crisis in myelogenous leukaemia	464.52	15.01	102	25320	564	42595349
Electrocardiogram QT prolonged	395.55	15.01	283	25139	47662	42548251
Second primary malignancy	392.83	15.01	164	25258	9411	42586502
Peripheral arterial occlusive disease	388.02	15.01	148	25274	6690	42589223
Drug resistance	295.82	15.01	208	25214	34040	42561873
Pleural effusion	270.74	15.01	311	25111	96855	42499058
Angina pectoris	250.25	15.01	185	25237	32711	42563202
Myocardial infarction	232.77	15.01	326	25096	123683	42472230
Intermittent claudication	220.00	15.01	75	25347	2440	42593473
Off label use	217.58	15.01	57	25365	638278	41957635
Drug intolerance	216.49	15.01	253	25169	80171	42515742
Philadelphia chromosome positive	203.90	15.01	52	25370	589	42595324
Death	174.52	15.01	645	24777	470540	42125373
Rash	162.73	15.01	445	24977	276509	42319404
Lipase increased	161.09	15.01	92	25330	10474	42585439
Chronic myeloid leukaemia transformation	140.14	15.01	31	25391	178	42595735
Coronary artery stenosis	136.17	15.01	82	25340	10297	42585616
Chronic myeloid leukaemia recurrent	117.66	15.01	28	25394	232	42595681
Blood bilirubin increased	113.67	15.01	133	25289	42119	42553794
Acute myocardial infarction	113.50	15.01	156	25266	58009	42537904
Pancreatitis	107.84	15.01	131	25291	43137	42552776
Myocardial ischaemia	106.90	15.01	87	25335	17675	42578238
Malignant neoplasm progression	106.03	15.01	213	25209	108187	42487726
Peripheral artery stenosis	103.22	15.01	33	25389	874	42595039
White blood cell count increased	98.80	15.01	128	25294	44959	42550954
Coronary artery disease	98.72	15.01	140	25282	53580	42542333
Carotid artery stenosis	95.59	15.01	52	25370	5384	42590529
Arterial disorder	95.55	15.01	34	25388	1258	42594655
Peripheral vascular disorder	93.88	15.01	51	25371	5266	42590647
Acute kidney injury	87.24	15.01	56	25366	367281	42228632
Gene mutation identification test positive	84.98	15.01	21	25401	207	42595706
Platelet count decreased	81.37	15.01	223	25199	138358	42457555
Acute coronary syndrome	75.42	15.01	66	25356	14799	42581114
Hypotension	70.19	15.01	33	25389	257598	42338315
Abdominal pain upper	69.84	15.01	153	25269	82456	42513457
Chest pain	67.91	15.01	210	25212	139320	42456593
Blast cell crisis	65.01	15.01	15	25407	107	42595806
Concomitant disease progression	64.54	15.01	31	25391	2472	42593441
Thrombocytopenia	63.69	15.01	253	25169	190026	42405887
Splenomegaly	62.13	15.01	63	25359	16984	42578929
Concomitant disease aggravated	61.47	15.01	42	25380	6544	42589369
Toxicity to various agents	61.40	15.01	30	25392	229106	42366807
Peripheral artery occlusion	60.78	15.01	27	25395	1799	42594114
Loss of therapeutic response	59.33	15.01	24	25398	1267	42594646
Arterial stenosis	57.74	15.01	23	25399	1166	42594747
Polymerase chain reaction positive	56.93	15.01	14	25408	135	42595778
Arteriosclerosis	55.79	15.01	61	25361	17928	42577985
Bone pain	52.80	15.01	68	25354	23724	42572189
Cerebral artery stenosis	52.26	15.01	16	25406	366	42595547
Angina unstable	50.53	15.01	47	25375	11401	42584512
Cerebral infarction	49.67	15.01	76	25346	31093	42564820
Condition aggravated	49.01	15.01	50	25372	260704	42335209
Exposure via father	47.12	15.01	12	25410	135	42595778
Myalgia	46.13	15.01	144	25278	95936	42499977
Chronic myeloid leukaemia	44.26	15.01	24	25398	2468	42593445
Labelled drug-food interaction medication error	42.97	15.01	9	25413	38	42595875
Cerebrovascular accident	40.69	15.01	139	25283	97021	42498892
Peripheral ischaemia	39.50	15.01	32	25390	6453	42589460
Confusional state	39.06	15.01	26	25396	167571	42428342
Overdose	38.36	15.01	8	25414	105256	42490657
Pericardial effusion	37.94	15.01	65	25357	29210	42566703
Infarction	37.29	15.01	23	25399	3012	42592901
Hypercholesterolaemia	37.14	15.01	42	25380	12807	42583106
Acoustic neuroma	37.13	15.01	10	25412	142	42595771
Gene mutation	36.87	15.01	19	25403	1762	42594151
Therapeutic response decreased	35.24	15.01	72	25350	36940	42558973
Leukocytosis	34.67	15.01	63	25359	29645	42566268
Amylase increased	34.37	15.01	30	25392	6699	42589214
Hyperglycaemia	34.35	15.01	81	25341	45778	42550135
Blood glucose increased	32.22	15.01	107	25315	73592	42522321
Carotid arteriosclerosis	32.07	15.01	19	25403	2313	42593600
Coronary artery occlusion	30.18	15.01	35	25387	10962	42584951
Fall	30.08	15.01	59	25363	234461	42361452
Drug hypersensitivity	29.80	15.01	11	25411	99378	42496535
Drug interaction	29.46	15.01	73	25349	266926	42328987
Treatment failure	29.25	15.01	93	25329	62531	42533382
Pruritus	28.82	15.01	202	25220	188569	42407344
Tremor	28.61	15.01	11	25411	96918	42498995
Arterial thrombosis	28.50	15.01	16	25406	1760	42594153
Muscle spasms	27.58	15.01	113	25309	85931	42509982
Hyponatraemia	27.57	15.01	13	25409	101449	42494464
Pulmonary hypertension	27.53	15.01	50	25372	23519	42572394
Cytopenia	26.94	15.01	42	25380	17455	42578458
Ischaemia	26.79	15.01	23	25399	5024	42590889
Fatigue	26.52	15.01	385	25037	435256	42160657
Gangrene	26.48	15.01	23	25399	5103	42590810
Haematotoxicity	25.32	15.01	32	25390	10953	42584960
Paternal exposure during pregnancy	25.21	15.01	7	25415	112	42595801
Myopathy toxic	24.80	15.01	11	25411	730	42595183
Oedematous pancreatitis	24.52	15.01	11	25411	750	42595163
Product blister packaging issue	24.39	15.01	7	25415	127	42595786
Clonal evolution	24.34	15.01	7	25415	128	42595785
Intentional product misuse	24.05	15.01	4	25418	61896	42534017
Hallucination	24.01	15.01	3	25419	57504	42538409
Dehydration	23.53	15.01	30	25392	141737	42454176
Cardiovascular disorder	23.30	15.01	34	25388	13331	42582582
Arterial occlusive disease	23.04	15.01	20	25402	4433	42591480
Gamma-glutamyltransferase increased	22.82	15.01	56	25366	32441	42563472
Karyotype analysis abnormal	22.76	15.01	6	25416	78	42595835
Febrile neutropenia	22.71	15.01	48	25374	185655	42410258
Asthma	22.16	15.01	5	25417	62309	42533604
Acquired gene mutation	22.06	15.01	13	25409	1567	42594346
Diabetes mellitus	21.75	15.01	82	25340	60005	42535908
Blast cells present	21.74	15.01	9	25413	504	42595409
Pain in extremity	21.71	15.01	159	25263	150445	42445468
Arteritis	21.69	15.01	9	25413	507	42595406
Atrial fibrillation	21.65	15.01	150	25272	139443	42456470
Headache	21.64	15.01	228	25194	239141	42356772
Agitation	21.25	15.01	6	25416	64308	42531605
Bone marrow failure	21.13	15.01	55	25367	33038	42562875
Haemoglobin decreased	20.93	15.01	143	25279	132328	42463585
Intentional overdose	20.73	15.01	3	25419	51453	42544460
Chloroma	20.72	15.01	9	25413	568	42595345
Central nervous system leukaemia	20.48	15.01	8	25414	385	42595528
Pulmonary embolism	20.17	15.01	25	25397	119587	42476326
Leukaemia recurrent	20.01	15.01	13	25409	1863	42594050
Loss of personal independence in daily activities	19.85	15.01	3	25419	49813	42546100
Angiopathy	19.82	15.01	20	25402	5357	42590556
Necrosis	19.66	15.01	22	25400	6629	42589284
Gelatinous transformation of the bone marrow	19.48	15.01	4	25418	15	42595898
Hepatotoxicity	19.43	15.01	45	25377	25122	42570791
Somnolence	19.40	15.01	34	25388	141071	42454842
Pancreatic fibrosis	19.28	15.01	3	25419	0	42595913
Oncologic complication	19.21	15.01	8	25414	455	42595458
Delirium	19.11	15.01	4	25418	52515	42543398
Abdominal pain	18.43	15.01	184	25238	190287	42405626
Basophil count increased	18.28	15.01	9	25413	757	42595156
Alopecia	18.02	15.01	48	25374	29228	42566685
Oxygen saturation decreased	18.02	15.01	8	25414	64679	42531234
Myeloproliferative neoplasm	17.95	15.01	9	25413	788	42595125
Vascular stenosis	17.90	15.01	6	25416	185	42595728
Rectosigmoid cancer	17.87	15.01	6	25416	186	42595727
B-cell small lymphocytic lymphoma	17.78	15.01	6	25416	189	42595724
Chest discomfort	17.65	15.01	80	25342	63536	42532377
Pancreatic enzymes increased	17.05	15.01	9	25413	876	42595037
Intentional product use issue	16.91	15.01	11	25411	71822	42524091
Platelet count increased	16.90	15.01	26	25396	10677	42585236
Cytogenetic response	16.74	15.01	3	25419	4	42595909
Wheezing	16.52	15.01	6	25416	54775	42541138
Blood bilirubin unconjugated increased	16.10	15.01	8	25414	687	42595226
Vertebral artery occlusion	16.04	15.01	6	25416	256	42595657
Rheumatoid arthritis	15.93	15.01	3	25419	42437	42553476
Blood creatine phosphokinase increased	15.89	15.01	64	25358	48274	42547639
Neoplasm malignant	15.76	15.01	39	25383	22704	42573209
Gait apraxia	15.67	15.01	3	25419	7	42595906
Arrhythmia	15.41	15.01	56	25366	40261	42555652
Renal artery stenosis	15.32	15.01	12	25410	2305	42593608
Transformation to acute myeloid leukaemia	15.19	15.01	9	25413	1096	42594817
Pancreatic toxicity	15.18	15.01	4	25418	52	42595861
Metabolic acidosis	15.10	15.01	6	25416	51852	42544061

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
Cytogenetic analysis abnormal	907.81	15.38	177	33596	1092	110554434
Blast crisis in myelogenous leukaemia	543.03	15.38	111	33662	897	110554629
Peripheral arterial occlusive disease	500.70	15.38	163	33610	9117	110546409
Electrocardiogram QT prolonged	484.88	15.38	340	33433	108620	110446906
Drug resistance	458.51	15.38	258	33515	56116	110499410
Second primary malignancy	446.30	15.38	178	33595	17890	110537636
Pleural effusion	417.36	15.38	381	33392	177328	110378198
Philadelphia chromosome positive	334.84	15.38	73	33700	827	110554699
Lipase increased	301.32	15.38	136	33637	18536	110536990
Chronic myeloid leukaemia transformation	286.63	15.38	54	33719	269	110555257
Myocardial infarction	280.87	15.38	319	33454	191764	110363762
Blood bilirubin increased	220.60	15.38	184	33589	75788	110479738
Intermittent claudication	220.02	15.38	70	33703	3631	110551895
Death	205.26	15.38	570	33203	698299	109857227
Angina pectoris	204.31	15.38	162	33611	62133	110493393
Off label use	194.46	15.38	109	33664	1500076	109055450
Platelet count decreased	191.74	15.38	290	33483	230153	110325373
Rash	187.73	15.38	613	33160	820351	109735175
Acute myocardial infarction	187.40	15.38	175	33598	83602	110471924
Malignant neoplasm progression	162.96	15.38	232	33541	174335	110381191
Peripheral artery stenosis	152.51	15.38	42	33731	1312	110554214
Carotid artery stenosis	147.93	15.38	67	33706	9196	110546330
Chronic myeloid leukaemia recurrent	135.47	15.38	30	33743	367	110555159
Myocardial ischaemia	132.02	15.38	89	33684	26595	110528931
Thrombocytopenia	129.32	15.38	311	33462	348574	110206952
Pancreatitis	127.56	15.38	150	33623	93383	110462143
White blood cell count increased	126.62	15.38	152	33621	96690	110458836
Bone pain	124.81	15.38	125	33648	65008	110490518
Myalgia	117.65	15.38	229	33544	222152	110333374
Acute coronary syndrome	111.75	15.38	76	33697	23036	110532490
Coronary artery stenosis	106.45	15.38	61	33712	13697	110541829
Arterial disorder	103.75	15.38	35	33738	2184	110553342
Gene mutation identification test positive	103.44	15.38	23	33750	287	110555239
Coronary artery disease	101.12	15.38	117	33656	71573	110483953
Arteriosclerosis	91.16	15.38	69	33704	24698	110530828
Cerebral infarction	89.37	15.38	94	33679	51744	110503782
Splenomegaly	87.42	15.38	67	33706	24431	110531095
Pericardial effusion	86.83	15.38	97	33676	57120	110498406
Peripheral vascular disorder	85.62	15.38	45	33728	8531	110546995
Condition aggravated	79.25	15.38	65	33708	734771	109820755
Polymerase chain reaction positive	79.11	15.38	19	33754	339	110555187
Blood glucose increased	76.89	15.38	142	33631	132354	110423172
Joint swelling	75.32	15.38	21	33752	442824	110112702
Rheumatoid arthritis	72.08	15.38	5	33768	299608	110255918
Drug intolerance	71.43	15.38	279	33494	406233	110149293
Acute lymphocytic leukaemia recurrent	71.29	15.38	35	33738	5752	110549774
Amylase increased	69.80	15.38	45	33728	12474	110543052
Chronic myeloid leukaemia	68.52	15.38	31	33742	4242	110551284
Pancytopenia	67.22	15.38	177	33596	209436	110346090
Hyperbilirubinaemia	66.49	15.38	63	33710	30608	110524918
Bone marrow failure	66.27	15.38	85	33688	57763	110497763
Hypotension	66.15	15.38	39	33734	523810	110031716
Haemoglobin decreased	65.97	15.38	196	33577	248531	110306995
Cerebral artery stenosis	65.87	15.38	20	33753	887	110554639
Hyperglycaemia	64.92	15.38	103	33670	84987	110470539
Cerebrovascular accident	63.21	15.38	158	33615	181126	110374400
Peripheral artery occlusion	62.72	15.38	26	33747	2879	110552647
Drug hypersensitivity	61.41	15.38	31	33742	454059	110101467
Haematotoxicity	61.02	15.38	51	33722	21031	110534495
Concomitant disease progression	60.47	15.38	27	33746	3583	110551943
Confusional state	59.01	15.38	35	33738	468645	110086881
Concomitant disease aggravated	58.92	15.38	45	33728	16319	110539207
Blast cell crisis	58.63	15.38	13	33760	160	110555366
Arterial stenosis	58.23	15.38	21	33752	1598	110553928
Gamma-glutamyltransferase increased	56.42	15.38	81	33692	61228	110494298
Cytopenia	56.21	15.38	57	33716	30059	110525467
Arthropathy	56.17	15.38	10	33763	287512	110268014
Acute kidney injury	56.04	15.38	67	33706	635363	109920163
Amaurosis fugax	53.67	15.38	22	33751	2368	110553158
Pruritus	52.40	15.38	330	33443	581230	109974296
Platelet count increased	51.27	15.38	51	33722	26283	110529243
Peripheral ischaemia	50.23	15.38	35	33738	11023	110544503
Glossodynia	49.82	15.38	5	33768	221999	110333527
Wheezing	49.59	15.38	9	33764	255221	110300305
Therapeutic response decreased	49.30	15.38	98	33675	96401	110459125
Gene mutation	49.11	15.38	23	33750	3406	110552120
Atrial fibrillation	49.04	15.38	168	33605	229474	110326052
Psoriatic arthropathy	48.15	15.38	3	33770	196758	110358768
Anaemia	47.15	15.38	307	33466	546779	110008747
Chest pain	46.08	15.38	232	33541	376143	110179383
Leukocytosis	45.03	15.38	68	33705	53760	110501766
Acquired gene mutation	44.22	15.38	20	33753	2734	110552792
Toxicity to various agents	43.06	15.38	50	33723	480505	110075021
Mobility decreased	42.75	15.38	10	33763	237412	110318114
Therapeutic response delayed	42.50	15.38	16	33757	1374	110554152
Cardiac failure	42.47	15.38	140	33633	187486	110368040
Overdose	41.80	15.38	10	33763	233784	110321742
Hypersensitivity	40.73	15.38	38	33735	403960	110151566
Sinusitis	40.46	15.38	20	33753	296668	110258858
Thrombocytosis	40.44	15.38	30	33743	10414	110545112
Lower respiratory tract infection	40.43	15.38	12	33761	243094	110312432
Angina unstable	39.97	15.38	36	33737	16396	110539130
Loss of therapeutic response	39.58	15.38	18	33755	2492	110553034
Abdominal pain	39.48	15.38	280	33493	512709	110042817
Leukaemia recurrent	38.76	15.38	19	33754	3112	110552414
Musculoskeletal stiffness	37.95	15.38	19	33754	279803	110275723
Diabetes mellitus	37.15	15.38	89	33684	99292	110456234
Exposure during pregnancy	36.97	15.38	4	33769	167420	110388106
Hepatic function abnormal	36.70	15.38	83	33690	89212	110466314
Ill-defined disorder	36.62	15.38	3	33770	156850	110398676
Intentional product use issue	36.48	15.38	15	33758	247891	110307635
Angiopathy	35.89	15.38	26	33747	8704	110546822
Stomatitis	35.68	15.38	19	33754	270223	110285303
Asthma	35.47	15.38	16	33757	250275	110305251
Abdominal pain upper	35.13	15.38	204	33569	348907	110206619
Keratosis pilaris	34.93	15.38	8	33765	115	110555411
Alanine aminotransferase increased	34.57	15.38	129	33644	183644	110371882
Infarction	34.56	15.38	21	33752	5248	110550278
Hepatotoxicity	33.11	15.38	65	33708	63335	110492191
Arterial occlusive disease	32.33	15.38	31	33742	15277	110540249
Acne	31.89	15.38	45	33728	33475	110522051
Palpitations	31.83	15.38	114	33659	159098	110396428
Discomfort	31.57	15.38	13	33760	214694	110340832
Blood lactate dehydrogenase increased	31.54	15.38	52	33721	44282	110511244
White blood cell count decreased	31.35	15.38	146	33627	229244	110326282
Gangrene	30.62	15.38	31	33742	16310	110539216
Wound	30.20	15.38	17	33756	234420	110321106
Clonal evolution	29.23	15.38	8	33765	244	110555282
Karyotype analysis abnormal	28.97	15.38	6	33767	52	110555474
Helicobacter infection	28.43	15.38	10	33763	181867	110373659
Product use issue	28.36	15.38	32	33741	311663	110243863
Coronary artery occlusion	27.89	15.38	29	33744	15743	110539783
Myelofibrosis	27.62	15.38	15	33758	3036	110552490
Ischaemic stroke	27.49	15.38	47	33726	41216	110514310
Transformation to acute myeloid leukaemia	27.47	15.38	12	33761	1511	110554015
Xanthelasma	27.42	15.38	7	33766	162	110555364
Generalised oedema	27.42	15.38	40	33733	30664	110524862
Intentional product misuse	27.34	15.38	4	33769	132900	110422626
Chylothorax	27.19	15.38	11	33762	1145	110554381
Blood creatine phosphokinase increased	26.83	15.38	65	33708	73012	110482514
Central nervous system leukaemia	26.37	15.38	9	33764	582	110554944
Labelled drug-food interaction medication error	25.91	15.38	7	33766	203	110555323
Dyslipidaemia	25.83	15.38	28	33745	15937	110539589
Delirium	25.71	15.38	5	33768	135020	110420506
Cytogenetic response	25.61	15.38	4	33769	4	110555522
Ocular discomfort	25.43	15.38	21	33752	8512	110547014
Pancreatic toxicity	25.31	15.38	6	33767	101	110555425
Hyponatraemia	24.99	15.38	18	33755	217635	110337891
Vertebral artery stenosis	24.87	15.38	7	33766	237	110555289
Arterial thrombosis	24.58	15.38	14	33759	3105	110552421
Swelling	24.08	15.38	44	33729	350997	110204529
Oxygen saturation decreased	23.91	15.38	9	33764	156973	110398553
Osteoarthritis	23.87	15.38	13	33760	182610	110372916
Basophilia	23.78	15.38	5	33768	47	110555479
Urticaria	23.67	15.38	38	33735	318819	110236707
Transient ischaemic attack	23.59	15.38	57	33716	63925	110491601
Blast cell count increased	23.51	15.38	11	33762	1626	110553900
Pulmonary hypertension	23.44	15.38	52	33721	55168	110500358
Acoustic neuroma	23.04	15.38	7	33766	311	110555215
Impaired healing	22.94	15.38	16	33757	196701	110358825
Pancreatic enzymes increased	22.93	15.38	11	33762	1718	110553808
Chronic myeloid leukaemia (in remission)	22.84	15.38	4	33769	12	110555514
Injury	22.62	15.38	13	33760	177252	110378274
Irritable bowel syndrome	22.48	15.38	11	33762	164204	110391322
Basophil count increased	22.45	15.38	11	33762	1799	110553727
Pain in extremity	21.79	15.38	236	33537	486882	110068644
Haemolytic transfusion reaction	21.75	15.38	4	33769	17	110555509
Skin toxicity	21.44	15.38	22	33751	11761	110543765
Peripheral artery thrombosis	21.29	15.38	14	33759	4010	110551516
Dry mouth	21.10	15.38	18	33755	199930	110355596
Exposure via father	20.83	15.38	5	33768	89	110555437
Cardiovascular disorder	20.83	15.38	30	33743	22730	110532796
Product use in unapproved indication	20.56	15.38	69	33704	447308	110108218
Aspartate aminotransferase increased	20.54	15.38	100	33673	159836	110395690
Vascular stenosis	20.37	15.38	8	33765	770	110554756
Oedematous pancreatitis	20.36	15.38	10	33763	1644	110553882
Blood bilirubin unconjugated increased	20.32	15.38	9	33764	1172	110554354
Necrosis	20.22	15.38	21	33752	11385	110544141
Vertebral artery occlusion	19.90	15.38	7	33766	495	110555031
Chloroma	19.70	15.38	8	33765	840	110554686
Remission not achieved	19.57	15.38	7	33766	520	110555006
Chromosome analysis abnormal	19.49	15.38	6	33767	279	110555247
Myopathy toxic	19.32	15.38	9	33764	1316	110554210
Suicide attempt	19.32	15.38	4	33769	103390	110452136
Pyrexia	19.32	15.38	383	33390	897882	109657644
Pleurisy	19.16	15.38	21	33752	12095	110543431
Neoplasm progression	19.12	15.38	53	33720	64542	110490984
Folliculitis	19.07	15.38	14	33759	167639	110387887
Moyamoya disease	18.96	15.38	5	33768	132	110555394
Dry skin	18.94	15.38	74	33699	107579	110447947
Jaundice	18.94	15.38	50	33723	59186	110496340
Skin disorder	18.88	15.38	41	33732	42872	110512654
Myeloproliferative neoplasm	18.82	15.38	9	33764	1396	110554130
Urinary tract disorder	18.72	15.38	15	33758	5829	110549697
Pancreatitis acute	18.39	15.38	50	33723	60224	110495302
Obesity	18.11	15.38	6	33767	113345	110442181
Adverse drug reaction	17.93	15.38	5	33768	105554	110449972
Therapy non-responder	17.85	15.38	95	33678	157212	110398314
Liver injury	17.84	15.38	12	33761	150401	110405125
Cerebrovascular stenosis	17.78	15.38	5	33768	169	110555357
Fall	17.61	15.38	110	33663	603372	109952154
Skin sensitisation	17.57	15.38	8	33765	1111	110554415
Muscle spasms	17.53	15.38	145	33628	278012	110277514
Renal artery stenosis	17.41	15.38	12	33761	3714	110551812
Diplopia	17.27	15.38	39	33734	41855	110513671
Therapeutic product effect incomplete	17.25	15.38	26	33747	223779	110331747
Drug ineffective for unapproved indication	17.23	15.38	5	33768	102833	110452693
Extremity necrosis	17.19	15.38	12	33761	3790	110551736
Splenitis	17.13	15.38	3	33770	9	110555517
Blood alkaline phosphatase increased	17.00	15.38	54	33719	70881	110484645
Psoriasis	16.84	15.38	11	33762	139982	110415544
Suicidal ideation	16.82	15.38	4	33769	93933	110461593
Acute lymphocytic leukaemia	16.79	15.38	14	33759	5751	110549775
Myelodysplastic syndrome	16.70	15.38	36	33737	37448	110518078
Graft versus host disease in eye	16.67	15.38	6	33767	454	110555072
General physical health deterioration	16.67	15.38	70	33703	425225	110130301
Vaginal odour	16.58	15.38	6	33767	461	110555065
Paternal exposure during pregnancy	16.46	15.38	5	33768	222	110555304
Vertebral artery hypoplasia	16.46	15.38	3	33770	12	110555514
Supraventricular extrasystoles	16.39	15.38	16	33757	8057	110547469
Agitation	16.37	15.38	7	33766	113044	110442482
Musculoskeletal toxicity	16.31	15.38	5	33768	229	110555297
Peripheral venous disease	16.25	15.38	3	33770	84114	110471412
Tremor	16.06	15.38	23	33750	202209	110353317
Recurrent cancer	15.94	15.38	11	33762	3412	110552114
Dyslalia	15.88	15.38	8	33765	1389	110554137
Red blood cell count decreased	15.63	15.38	50	33723	65873	110489653
Peripheral swelling	15.52	15.38	67	33706	403967	110151559
Therapy cessation	15.51	15.38	39	33734	44818	110510708

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EA03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS BCR-ABL tyrosine kinase inhibitors
FDA MoA	N0000020009	Bcr-Abl Tyrosine Kinase Inhibitors
MeSH PA	D000092004	Tyrosine Kinase Inhibitors
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000182137	Cytochrome P450 2D6 Inhibitors
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000187062	Cytochrome P450 2C8 Inhibitors
FDA MoA	N0000187063	Cytochrome P450 2C8 Inducers
FDA MoA	N0000187064	Cytochrome P450 2B6 Inducers
FDA MoA	N0000191272	UGT1A1 Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agent
CHEBI has role	CHEBI:35674	antihypertensive agent
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitor
CHEBI has role	CHEBI:48407	antiparkinson drug
CHEBI has role	CHEBI:149553	anticoronaviral agent

Related Drugs by ATC class:

L01EA BCR-ABL tyrosine kinase inhibitors 5 drugs

asciminib bosutinib dasatinib imatinib ponatinib

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

Disease	Relation	SNOMED_ID	DOID
Chronic phase chronic myeloid leukemia	indication	413847001
Philadelphia Chromosome Positive Chronic Myelocytic Leukemia	indication
Chronic Myelocytic Leukemia Accelerated Phase	indication
Hypophosphatemia	contraindication	4996001
Hypocalcemia	contraindication	5291005
Hypercholesterolemia	contraindication	13644009
Hyperkalemia	contraindication	14140009
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Torsades de pointes	contraindication	31722008
Hypertensive disorder	contraindication	38341003	DOID:10763
Hypokalemia	contraindication	43339004
Gastrectomy	contraindication	53442002
Diabetes mellitus	contraindication	73211009	DOID:9351
Pancreatitis	contraindication	75694006	DOID:4989
Hyperglycemia	contraindication	80394007	DOID:4195
Hyponatremia	contraindication	89627008
Prolonged QT interval	contraindication	111975006
Liver function tests abnormal	contraindication	166603001
Hypomagnesemia	contraindication	190855004
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Breastfeeding (mother)	contraindication	413712001
Congenital long QT syndrome	contraindication	442917000
Elevated Serum Lipase	contraindication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.89	acidic
pKa2	6.03	Basic
pKa3	3.97	Basic
pKa4	2.2	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 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	8389537	July 18, 2026	TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	8415363	July 18, 2026	TREATMENT OF NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH + CML)
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	8415363	July 18, 2026	TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	9061029	April 7, 2032	TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML)
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	9061029	April 7, 2032	TREATMENT OF PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+CML) BY ADMINISTERING NILOTINIB DISPERSED IN A FRUIT PREPARATION
60MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	11389450	Jan. 29, 2041	USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
60MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	11389450	Jan. 29, 2041	USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
60MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	12016861	Jan. 29, 2041	USE OF 120 MG NILOTINIB TWICE DAILY FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE
60MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	12016861	Jan. 29, 2041	USE OF 160 MG NILOTINIB TWICE DAILY FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB
80MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	11389450	Jan. 29, 2041	USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
80MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	11389450	Jan. 29, 2041	USE OF NILOTINIB FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE, WHEN ADMINISTERED WITH FOOD OR IN FED STATE
80MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	12016861	Jan. 29, 2041	USE OF 120 MG NILOTINIB TWICE DAILY FOR TREATMENT OF ADULT PATIENTS WITH NEWLY DIAGNOSED PH+ CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE
80MG	CAVHANZA	FLEX PHARMA	N217379	May 29, 2026	RX	TABLET, ORALLY DISINTEGRATING	ORAL	12016861	Jan. 29, 2041	USE OF 160 MG NILOTINIB TWICE DAILY FOR TREATMENT OF ADULT PATIENTS WITH CHRONIC PHASE AND ACCELERATED PHASE PH+ CHRONIC MYELOID LEUKEMIA RESISTANT TO OR INTOLERANT TO PRIOR THERAPY THAT INCLUDED IMATINIB

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	Sept. 23, 2028	TREATMENT OF PEDIATRIC PATIENTS GREATER THAN OR EQUAL TO 1 YEAR OF AGE WITH ACCELERATED PHASE PHILADELPHIA CHROMOSOME POSITIVE CHRONIC MYELOID LEUKEMIA (PH+ CML) WITH RESISTANCE OR INTOLERANCE TO PRIOR TYROSINE-KINASE INHIBITOR (TKI) THERAPY
EQ 50MG BASE	TASIGNA	NOVARTIS	N022068	March 22, 2018	RX	CAPSULE	ORAL	March 23, 2029	PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN	INHIBITOR	Kd	8.44	CHEMBL	CHEMBL
Mitogen-activated protein kinase 14	Kinase	Q16539	MK14_HUMAN		Kd	6.34	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	6.35	CHEMBL
Carbonic anhydrase 2	Enzyme	P00918	CAH2_HUMAN		Ki	8.39	CHEMBL
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	5.60	CHEMBL
Carbonic anhydrase 1	Enzyme	P00915	CAH1_HUMAN		Ki	7.53	CHEMBL
Carbonic anhydrase 4	Enzyme	P22748	CAH4_HUMAN		Ki	6.35	CHEMBL
Ribosyldihydronicotinamide dehydrogenase [quinone]	Enzyme	P16083	NQO2_HUMAN		IC50	6.42	CHEMBL
Carbonic anhydrase 9	Enzyme	Q16790	CAH9_HUMAN		Ki	7.38	CHEMBL
Carbonic anhydrase 12	Enzyme	O43570	CAH12_HUMAN		Ki	6.52	CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN		Kd	7.80	CHEMBL
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN		Kd	7.77	CHEMBL
Carbonic anhydrase 5A, mitochondrial	Enzyme	P35218	CAH5A_HUMAN		Ki	5.26	CHEMBL
Carbonic anhydrase 5B, mitochondrial	Enzyme	Q9Y2D0	CAH5B_HUMAN		Ki	4.83	CHEMBL
Carbonic anhydrase 7	Enzyme	P43166	CAH7_HUMAN		Ki	7	CHEMBL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		Kd	5.72	CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	7.33	CHEMBL
Tyrosine-protein kinase Yes	Kinase	P07947	YES_HUMAN		Kd	5.96	CHEMBL
Tyrosine-protein kinase Fyn	Kinase	P06241	FYN_HUMAN		Kd	5.80	CHEMBL
Ephrin type-A receptor 2	Kinase	P29317	EPHA2_HUMAN		Kd	6.64	CHEMBL
RAF proto-oncogene serine/threonine-protein kinase	Kinase	P04049	RAF1_HUMAN		Kd	5.41	CHEMBL
Serine/threonine-protein kinase B-raf	Kinase	P15056	BRAF_HUMAN		Kd	6.24	CHEMBL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN		Kd	4.40	CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN		Kd	6.06	CHEMBL
Macrophage colony-stimulating factor 1 receptor	Kinase	P07333	CSF1R_HUMAN		Kd	7.35	CHEMBL
Platelet-derived growth factor receptor alpha	Kinase	P16234	PGFRA_HUMAN		Kd	7.13	CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	Kinase	P15735	PHKG2_HUMAN		Kd	6.48	CHEMBL
Insulin receptor	Kinase	P06213	INSR_HUMAN		Ki	5.39	PDSP
Mitogen-activated protein kinase 8	Kinase	P45983	MK08_HUMAN		Kd	6.35	CHEMBL
Tyrosine-protein kinase HCK	Kinase	P08631	HCK_HUMAN		Kd	6.41	CHEMBL
Carbonic anhydrase 3	Enzyme	P07451	CAH3_HUMAN		Ki	6.35	CHEMBL
Carbonic anhydrase 6	Enzyme	P23280	CAH6_HUMAN		Ki	6.34	CHEMBL
Mitogen-activated protein kinase 10	Kinase	P53779	MK10_HUMAN		Kd	5.70	CHEMBL
Tyrosine-protein kinase JAK2	Kinase	O60674	JAK2_HUMAN		Ki	5.07	PDSP
Tyrosine-protein kinase CSK	Kinase	P41240	CSK_HUMAN		Kd	5.62	CHEMBL
Angiopoietin-1 receptor	Kinase	Q02763	TIE2_HUMAN		Kd	6	CHEMBL
Ephrin type-A receptor 8	Kinase	P29322	EPHA8_HUMAN		Kd	7.43	CHEMBL
Tyrosine-protein kinase Lyn	Kinase	P07948	LYN_HUMAN		Kd	7	CHEMBL
Cytoplasmic tyrosine-protein kinase BMX	Kinase	P51813	BMX_HUMAN		Ki	5.32	PDSP
Carbonic anhydrase 14	Enzyme	Q9ULX7	CAH14_HUMAN		Ki	6.65	CHEMBL
Fibroblast growth factor receptor 1	Kinase	P11362	FGFR1_HUMAN		Ki	5.10	PDSP
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.17	CHEMBL
Abelson tyrosine-protein kinase 2	Kinase	P42684	ABL2_HUMAN		Kd	7.59	CHEMBL
Mitogen-activated protein kinase 11	Kinase	Q15759	MK11_HUMAN		Kd	7.44	CHEMBL
Ephrin type-A receptor 5	Kinase	P54756	EPHA5_HUMAN		Kd	5.72	CHEMBL
Ephrin type-A receptor 4	Kinase	P54764	EPHA4_HUMAN		Kd	6.48	CHEMBL
Fibroblast growth factor receptor 2	Kinase	P21802	FGFR2_HUMAN		Ki	5.14	PDSP
Ephrin type-A receptor 6	Kinase	Q9UF33	EPHA6_HUMAN		Kd	6.19	CHEMBL
Tyrosine-protein kinase Fgr	Kinase	P09769	FGR_HUMAN		Kd	6.49	CHEMBL
Ephrin type-A receptor 3	Kinase	P29320	EPHA3_HUMAN		Kd	6.96	CHEMBL
Dual specificity protein kinase CLK1	Kinase	P49759	CLK1_HUMAN		Kd	5.68	CHEMBL
Ephrin type-B receptor 1	Kinase	P54762	EPHB1_HUMAN		Kd	5.89	CHEMBL
Dual specificity protein kinase CLK4	Kinase	Q9HAZ1	CLK4_HUMAN		Kd	5.15	CHEMBL
Mitogen-activated protein kinase 9	Kinase	P45984	MK09_HUMAN		Kd	5.24	CHEMBL
Epithelial discoidin domain-containing receptor 1	Kinase	Q08345	DDR1_HUMAN		Kd	8.96	CHEMBL
Ephrin type-B receptor 4	Kinase	P54760	EPHB4_HUMAN		Kd	6.14	CHEMBL
BDNF/NT-3 growth factors receptor	Kinase	Q16620	NTRK2_HUMAN		Kd	6.31	CHEMBL
Ephrin type-B receptor 2	Kinase	P29323	EPHB2_HUMAN		Kd	6.19	CHEMBL
Mitogen-activated protein kinase kinase kinase MLT	Kinase	Q9NYL2	MLTK_HUMAN		Kd	7.96	CHEMBL
Tyrosine-protein kinase receptor Tie-1	Kinase	P35590	TIE1_HUMAN		Kd	6	CHEMBL
NT-3 growth factor receptor	Kinase	Q16288	NTRK3_HUMAN		Kd	6.22	CHEMBL
Serine/threonine-protein kinase TNNI3K	Kinase	Q59H18	TNI3K_HUMAN		Kd	6.44	CHEMBL
Discoidin domain-containing receptor 2	Kinase	Q16832	DDR2_HUMAN		Kd	8.22	CHEMBL
Mitogen-activated protein kinase kinase kinase kinase 1	Kinase	Q92918	M4K1_HUMAN		Kd	6.05	CHEMBL
Tyrosine-protein kinase Blk	Kinase	P51451	BLK_HUMAN		Kd	6.30	CHEMBL
Serine/threonine-protein kinase MRCK beta	Kinase	Q9Y5S2	MRCKB_HUMAN		Kd	6.04	CHEMBL
Ephrin type-A receptor 1	Kinase	P21709	EPHA1_HUMAN		Kd	6.23	CHEMBL
Ephrin type-B receptor 3	Kinase	P54753	EPHB3_HUMAN		Kd	6	CHEMBL
Ephrin type-B receptor 6	Kinase	O15197	EPHB6_HUMAN		Kd	6.30	CHEMBL
Serine/threonine-protein kinase TAO1	Kinase	Q7L7X3	TAOK1_HUMAN		Kd	5.33	CHEMBL
Serine/threonine-protein kinase TAO3	Kinase	Q9H2K8	TAOK3_HUMAN		Kd	5.77	CHEMBL
Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma	Kinase	Q8TBX8	PI42C_HUMAN		Kd	5.06	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	6.72	CHEMBL
Bcr/Abl fusion protein	Kinase	P00519 P11274	ABL1_HUMAN BCR_HUMAN		IC50	9.48	CHEMBL
Ferrochelatase, mitochondrial	Enzyme	P22830	HEMH_HUMAN		Kd	5.38	CHEMBL
Receptor-interacting serine/threonine-protein kinase 3	Kinase	Q9Y572	RIPK3_HUMAN		Kd	5.89	CHEMBL
Integrin-linked protein kinase	Kinase	Q13418	ILK_HUMAN		Kd	7.70	CHEMBL
Tyrosine-protein kinase FRK	Kinase	P42685	FRK_HUMAN		Kd	7.07	CHEMBL
Carbonic anhydrase 13	Enzyme		CAH13_MOUSE		Ki	5.33	CHEMBL
Carbonic anhydrase 15	Enzyme		CAH15_MOUSE		Ki	7.10	CHEMBL
Calcium-dependent protein kinase 1	Kinase		CDPK1_PLAF7		Kd	6.10	CHEMBL
Macrophage colony-stimulating factor 1 receptor	Kinase		CSF1R_MOUSE		IC50	6.27	CHEMBL

External reference:

ID	Source
4026964	VUID
N0000176124	NUI
D06413	KEGG_DRUG
4026964	VANDF
C1721377	UMLSCUI
CHEBI:52172	CHEBI
NIL	PDB_CHEM_ID
CHEMBL255863	ChEMBL_ID
CHEMBL1201740	ChEMBL_ID
DB04868	DRUGBANK_ID
C498826	MESH_SUPPLEMENTAL_RECORD_UI
5697	IUPHAR_LIGAND_ID
8654	INN_ID
923288-90-8	SECONDARY_CAS_RN
F41401512X	UNII
644241	PUBCHEM_CID
2701416	RXNORM
127956	MMSL
24733	MMSL
395040	MMSL
d07057	MMSL
012401	NDDF
427941004	SNOMEDCT_US
428468009	SNOMEDCT_US
438943005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Tasigna	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0526	CAPSULE	200 mg	ORAL	NDA	32 sections
Tasigna	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0592	CAPSULE	150 mg	ORAL	NDA	32 sections
Tasigna	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0951	CAPSULE	50 mg	ORAL	NDA	32 sections
nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	13668-710	CAPSULE	150 mg	ORAL	ANDA	26 sections
nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	13668-711	CAPSULE	200 mg	ORAL	ANDA	26 sections
DANZITEN	Human Prescription Drug Label	1	24338-154	TABLET	71 mg	ORAL	NDA	27 sections
DANZITEN	Human Prescription Drug Label	1	24338-155	TABLET	95 mg	ORAL	NDA	27 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	31722-779	CAPSULE	150 mg	ORAL	ANDA	28 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	31722-780	CAPSULE	200 mg	ORAL	ANDA	28 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	43598-055	CAPSULE	50 mg	ORAL	ANDA	31 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	43598-455	CAPSULE	150 mg	ORAL	ANDA	31 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	43598-456	CAPSULE	200 mg	ORAL	ANDA	31 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	60505-3801	CAPSULE	150 mg	ORAL	ANDA	26 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	60505-3802	CAPSULE	200 mg	ORAL	ANDA	26 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	60505-3803	CAPSULE	50 mg	ORAL	ANDA	26 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	69097-030	CAPSULE	50 mg	ORAL	NDA	32 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	69097-031	CAPSULE	150 mg	ORAL	NDA	32 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	69097-032	CAPSULE	200 mg	ORAL	NDA	32 sections
CAVHANZA	HUMAN PRESCRIPTION DRUG LABEL	1	70709-191	TABLET, ORALLY DISINTEGRATING	60 mg	ORAL	NDA	32 sections
CAVHANZA	HUMAN PRESCRIPTION DRUG LABEL	1	70709-192	TABLET, ORALLY DISINTEGRATING	80 mg	ORAL	NDA	32 sections
nilotinib	Human Prescription Drug Label	1	72205-237	CAPSULE	50 mg	ORAL	ANDA	25 sections
nilotinib	Human Prescription Drug Label	1	72205-238	CAPSULE	150 mg	ORAL	ANDA	25 sections
nilotinib	Human Prescription Drug Label	1	72205-239	CAPSULE	200 mg	ORAL	ANDA	25 sections
nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	73190-033	CAPSULE	150 mg	ORAL	ANDA	25 sections
nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	73190-034	CAPSULE	200 mg	ORAL	ANDA	25 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	76282-788	CAPSULE	50 mg	ORAL	NDA	32 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	76282-789	CAPSULE	150 mg	ORAL	NDA	32 sections
Nilotinib	HUMAN PRESCRIPTION DRUG LABEL	1	76282-790	CAPSULE	200 mg	ORAL	NDA	32 sections