Tox | Related Drugs | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	1548	231277-92-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: lapatinib tosilate hydrate lapatinib tosilate lapatinib GW 572016X tyverb lapatinib ditosylate GW572016F lapatinib ditosilate lapatinib ditosilate hydrate lapatinib ditosylate hydrate	A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2. Molecular weight: 581.06 Formula: C29H26ClFN4O4S CLOGP: 5.82 LIPINSKI: 2 HAC: 8 HDO: 2 TPSA: 106.35 ALOGS: -4.42 ROTB: 11 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

lapatinib tosilate hydrate
lapatinib tosilate
lapatinib
GW 572016X
tyverb
lapatinib ditosylate
GW572016F
lapatinib ditosilate
lapatinib ditosilate hydrate
lapatinib ditosylate hydrate

A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2.

Molecular weight: 581.06
Formula: C29H26ClFN4O4S
CLOGP: 5.82
LIPINSKI: 2
HAC: 8
HDO: 2
TPSA: 106.35
ALOGS: -4.42
ROTB: 11

Status: OFP

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

Drug dosage:

Dose	Unit	Route
1.25	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.00 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	1 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	30.73 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	24 %	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	4.298		High	1
caco2-efflux	Caco-2 efflux ratio (BA/AB)	41.495		High	1
caco2-intrinsic-papp	Caco-2 intrinsic apparent permeability	0.405	10^-6 cm/s	High	1
dh-clint	Dog hepatocyte intrinsic clearance	8.810	uL/min/10^6 cells	High	1
dppb	Dog plasma protein binding (% unbound)	0.280	%	High	1
fcs-ppb	Fetal calf serum protein binding (% unbound)	0.390	%	High	1
herg	hERG pIC50	4.961	pIC50	High	1
hh-clint	Human hepatocyte intrinsic clearance	23.605	uL/min/10^6 cells	High	1
hlm-clint	Human liver microsomal intrinsic clearance	59.429	uL/min/mg protein	High	1
hppb	Human plasma protein binding (% unbound)	0.260	%	High	1
mdck-mdr1-efflux	MDCK-MDR1 efflux ratio	38.019		High	1
mh-clint	Mouse hepatocyte intrinsic clearance	35.318		High	1
mppb	Mouse plasma protein binding (% unbound)	0.190		High	1
nih-mdck-mdr1-efflux	NIH MDCK-MDR1 efflux ratio	31.989		High	1
pfas-class	PFAS structural alert (1 = True, 0 = False)	0
pld-class	Phospholipidosis risk class (1 = positive, 0 = negative)	1		High	1
pppb	Pig plasma protein binding (% unbound)	0.280	%	High	1
rh-clint	Rat hepatocyte intrinsic clearance	64.269	uL/min/10^6 cells	High	1
rh-fuinc	Rat hepatocyte fraction unbound in incubation	0.520	%	High	1
rppb	Rat plasma protein binding (% unbound)	0.190	%	High	1
solubility-dd	Solubility at pH 7.4 in DMSO	0.869	uM	High	1

Approvals:

Date	Agency	Company	Orphan
June 10, 2008	EMA
March 13, 2007	FDA	NOVARTIS PHARMS CORP

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	2086.25	22.51	619	25331	27404	90575093
Diarrhoea	1620.20	22.51	1634	24316	937556	89664941
Disease progression	1062.37	22.51	621	25329	155994	90446503
Metastases to central nervous system	909.09	22.51	294	25656	17248	90585249
Malignant neoplasm progression	496.69	22.51	334	25616	106536	90495961
Paronychia	405.64	22.51	132	25818	7874	90594623
Neutropenia	380.69	22.51	391	25559	224513	90377984
Metastases to lung	326.73	22.51	135	25815	15856	90586641
Metastases to liver	323.12	22.51	160	25790	28647	90573850
Dehydration	293.12	22.51	318	25632	194129	90408368
Metastases to lymph nodes	274.24	22.51	109	25841	11580	90590917
Metastases to bone	269.34	22.51	136	25814	25369	90577128
Breast cancer metastatic	237.44	22.51	106	25844	15026	90587471
Ejection fraction decreased	234.18	22.51	125	25825	26128	90576369
Blood bilirubin increased	223.80	22.51	145	25805	43325	90559172
Vomiting	200.35	22.51	585	25365	787708	89814789
Skin toxicity	197.46	22.51	74	25876	6705	90595792
Death	196.69	22.51	415	25535	456136	90146361
Skin fissures	182.54	22.51	98	25852	20711	90581786
Jaundice	158.88	22.51	105	25845	32412	90570085
Metastases to skin	157.63	22.51	47	25903	2093	90600404
Mucosal inflammation	153.03	22.51	129	25821	57496	90545001
Hypokalaemia	124.64	22.51	170	25780	130946	90471551
Nausea	123.49	22.51	634	25316	1109682	89492815
Gastrointestinal toxicity	122.44	22.51	58	25892	9409	90593088
Hepatic function abnormal	121.61	22.51	103	25847	46185	90556312
Febrile neutropenia	115.25	22.51	181	25769	158168	90444329
Hepatotoxicity	108.27	22.51	96	25854	45746	90556751
Hyperbilirubinaemia	103.98	22.51	59	25891	13877	90588620
Alanine aminotransferase increased	102.85	22.51	147	25803	118191	90484306
Pleural effusion	101.60	22.51	142	25808	111849	90490648
Lymphangiosis carcinomatosa	98.78	22.51	31	25919	1641	90600856
Vascular device infection	98.44	22.51	54	25896	11898	90590599
Streptococcal sepsis	96.70	22.51	37	25913	3547	90598950
Haematotoxicity	96.04	22.51	54	25896	12481	90590016
Cardiotoxicity	95.31	22.51	52	25898	11337	90591160
Dry skin	92.58	22.51	120	25830	87953	90514544
Weight increased	87.62	22.51	9	25941	417918	90184579
Brain oedema	87.00	22.51	57	25893	17328	90585169
Joint swelling	84.91	22.51	20	25930	503280	90099217
Condition aggravated	83.69	22.51	33	25917	595512	90006985
Rash	80.87	22.51	444	25506	795656	89806841
Nail bed inflammation	80.40	22.51	27	25923	1774	90600723
Pseudomonal sepsis	80.06	22.51	34	25916	4268	90598229
Nasal mucosal disorder	79.59	22.51	27	25923	1830	90600667
Drug hypersensitivity	77.06	22.51	19	25931	463590	90138907
Asthenia	75.91	22.51	328	25622	533423	90069074
Pyrexia	75.70	22.51	381	25569	660104	89942393
Glossodynia	72.71	22.51	5	25945	321774	90280723
Arthralgia	69.99	22.51	72	25878	778450	89824047
Maternal exposure during pregnancy	69.94	22.51	10	25940	360053	90242444
Metastasis	68.51	22.51	34	25916	6103	90596394
Therapeutic product effect decreased	66.76	22.51	3	25947	277568	90324929
Neuropathy peripheral	63.97	22.51	129	25821	136841	90465656
Aspartate aminotransferase increased	60.55	22.51	107	25843	102830	90499667
Wound	59.80	22.51	8	25942	302972	90299525
Breast cancer	59.23	22.51	75	25875	53686	90548811
Dermatitis acneiform	58.74	22.51	31	25919	6323	90596174
Decreased appetite	58.60	22.51	238	25712	376302	90226195
Thrombocytopenia	58.51	22.51	161	25789	208564	90393933
Off label use	58.40	22.51	145	25805	1102107	89500390
Infusion related reaction	55.43	22.51	25	25925	416755	90185742
Sinusitis	55.18	22.51	15	25935	343073	90259424
Cellulitis	55.08	22.51	96	25854	91241	90511256
Neoplasm progression	52.10	22.51	64	25886	44422	90558075
Stomatitis	52.10	22.51	185	25765	274513	90327984
Musculoskeletal stiffness	51.53	22.51	11	25939	296521	90305976
Mobility decreased	50.99	22.51	6	25944	250728	90351769
Discomfort	50.15	22.51	9	25941	274326	90328171
Ascites	50.07	22.51	65	25885	47675	90554822
Leukopenia	49.59	22.51	97	25853	100613	90501884
Asthma	48.73	22.51	6	25944	242154	90360343
Hypertension	47.40	22.51	37	25913	457495	90145002
Second primary malignancy	47.04	22.51	32	25918	10346	90592151
Varicose vein	46.67	22.51	28	25922	7299	90595198
Type 2 diabetes mellitus	46.36	22.51	3	25947	203241	90399256
Superior vena cava syndrome	45.02	22.51	14	25936	719	90601778
Neurotoxicity	44.89	22.51	42	25908	21425	90581072
Recurrent cancer	44.32	22.51	19	25931	2440	90600057
Lower respiratory tract infection	44.16	22.51	9	25941	250650	90351847
Folliculitis	43.84	22.51	4	25946	204349	90398148
Anaemia	43.46	22.51	208	25742	352594	90249903
Botryomycosis	43.29	22.51	8	25942	38	90602459
Swelling	43.26	22.51	34	25916	419024	90183473
Metastatic neoplasm	43.12	22.51	23	25927	4792	90597705
Wheezing	43.10	22.51	8	25942	238072	90364425
Pericarditis	43.07	22.51	12	25938	270139	90332358
Biliary dilatation	42.54	22.51	19	25931	2692	90599805
Drug ineffective	42.28	22.51	229	25721	1384069	89218428
Gamma-glutamyltransferase increased	41.88	22.51	53	25897	37899	90564598
Breast neoplasm	41.51	22.51	16	25934	1564	90600933
Fall	40.51	22.51	47	25903	481763	90120734
Metastases to spine	39.61	22.51	20	25930	3723	90598774
Neoplasm	39.28	22.51	27	25923	8876	90593621
Pain	39.21	22.51	150	25800	996191	89606306
Onychalgia	38.78	22.51	14	25936	1140	90601357
Contusion	38.51	22.51	12	25938	251204	90351293
Transaminases	38.20	22.51	8	25942	79	90602418
Skin exfoliation	37.88	22.51	69	25881	67844	90534653
Breast cancer recurrent	37.58	22.51	22	25928	5481	90597016
Brain neoplasm	37.38	22.51	21	25929	4843	90597654
Eczema	36.43	22.51	59	25891	52811	90549686
Skin mass	36.29	22.51	24	25926	7406	90595091
Onycholysis	36.18	22.51	16	25934	2214	90600283
Abdominal discomfort	35.54	22.51	51	25899	477277	90125220
Exposure during pregnancy	35.46	22.51	12	25938	238398	90364099
Hepatic failure	35.43	22.51	50	25900	39678	90562819
Candida infection	35.13	22.51	46	25904	34011	90568486
Product dose omission issue	35.01	22.51	20	25930	291667	90310830
Central nervous system lesion	34.93	22.51	28	25922	11618	90590879
Impaired healing	34.47	22.51	12	25938	234187	90368310
Performance status decreased	34.31	22.51	19	25931	4261	90598236
Leukonychia	33.82	22.51	7	25943	65	90602432
Erythema	33.33	22.51	142	25808	229104	90373393
Intracranial pressure increased	33.27	22.51	22	25928	6789	90595708
Left ventricular dysfunction	33.20	22.51	30	25920	14639	90587858
Anal erythema	32.92	22.51	9	25941	292	90602205
Peripheral swelling	32.91	22.51	42	25908	413064	90189433
Nasopharyngitis	32.84	22.51	41	25909	407063	90195434
Epistaxis	32.60	22.51	74	25876	85051	90517446
Hormone receptor positive breast cancer	32.08	22.51	11	25939	770	90601727
Erysipelas	32.02	22.51	24	25926	9028	90593469
Psoriasis	31.40	22.51	3	25947	147751	90454746
Product use issue	31.30	22.51	29	25921	329890	90272607
Limbal stem cell deficiency	31.15	22.51	6	25944	37	90602460
Nail infection	30.95	22.51	15	25935	2557	90599940
Plantar erythema	30.93	22.51	8	25942	209	90602288
Pericardial effusion	30.86	22.51	45	25905	36788	90565709
Neoplasm malignant	30.75	22.51	43	25907	33837	90568660
Completed suicide	30.68	22.51	3	25947	145055	90457442
Subclavian vein thrombosis	30.57	22.51	14	25936	2102	90600395
Radiation necrosis	29.69	22.51	10	25940	663	90601834
Drug intolerance	29.37	22.51	52	25898	447539	90154958
Tumour marker increased	28.95	22.51	19	25931	5788	90596709
Gastrointestinal bacterial infection	28.60	22.51	11	25939	1069	90601428
Hypersensitivity	27.91	22.51	55	25895	454622	90147875
Alopecia	27.79	22.51	63	25887	495008	90107489
Neoplasm recurrence	27.60	22.51	15	25935	3244	90599253
Injury	27.55	22.51	11	25939	197338	90405159
Osteonecrosis of jaw	27.44	22.51	44	25906	39059	90563438
Pulmonary embolism	27.29	22.51	91	25859	130729	90471768
Brain cancer metastatic	27.20	22.51	7	25943	179	90602318
Injection site pain	27.15	22.51	8	25942	173691	90428806
Urticaria	26.81	22.51	30	25920	312704	90289793
Polyneuropathy	26.24	22.51	30	25920	19311	90583186
Treatment failure	26.22	22.51	29	25921	303899	90298598
Sleep disorder	26.11	22.51	12	25938	198018	90404479
Radiation pneumonitis	25.93	22.51	12	25938	1846	90600651
Arthritis	25.62	22.51	8	25942	167307	90435190
Feeling abnormal	25.60	22.51	8	25942	167227	90435270
Pneumonitis	24.78	22.51	45	25905	44125	90558372
Lung infiltration	24.72	22.51	26	25924	15256	90587241
Dyschezia	23.74	22.51	13	25937	2852	90599645
Ingrowing nail	23.73	22.51	13	25937	2854	90599643
Jaundice cholestatic	23.64	22.51	21	25929	10022	90592475
Depression	23.47	22.51	31	25919	300570	90301927
Osteoradionecrosis	23.45	22.51	6	25944	150	90602347
Restlessness	23.44	22.51	39	25911	35681	90566816
Rash pustular	23.39	22.51	19	25931	8030	90594467
Malignant pleural effusion	23.33	22.51	13	25937	2951	90599546
Drug interaction	23.17	22.51	27	25923	276426	90326071
Metastases to meninges	23.08	22.51	14	25936	3721	90598776

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
Duodenal ulcer perforation	49.11	32.41	11	1117	1765	42618442
Diarrhoea	45.59	32.41	58	1070	460791	42159416
Dehydration	36.43	32.41	30	1098	141737	42478470
Metastases to lung	36.27	32.41	13	1115	11411	42608796

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	1326.16	21.85	422	18147	40603	110530127
Diarrhoea	1088.90	21.85	1128	17441	1138377	109432353
Disease progression	695.70	21.85	459	18110	243575	110327155
Metastases to central nervous system	659.98	21.85	216	18353	22601	110548129
Malignant neoplasm progression	378.39	21.85	278	18291	174289	110396441
Metastases to lung	296.27	21.85	120	18449	22943	110547787
Paronychia	268.96	21.85	92	18477	10989	110559741
Metastases to lymph nodes	259.70	21.85	97	18472	14935	110555795
Metastases to liver	249.97	21.85	121	18448	35265	110535465
Breast cancer metastatic	237.34	21.85	84	18485	11097	110559633
Metastases to bone	214.74	21.85	105	18464	31267	110539463
Dehydration	191.45	21.85	235	18334	279276	110291454
Metastases to skin	169.57	21.85	45	18524	2254	110568476
Vomiting	164.38	21.85	425	18144	910250	109660480
Ejection fraction decreased	164.33	21.85	96	18473	40784	110529946
Skin fissures	147.11	21.85	75	18494	24383	110546347
Neutropenia	143.78	21.85	239	18330	374381	110196349
Gastrointestinal toxicity	126.14	21.85	53	18516	11095	110559635
Blood bilirubin increased	116.82	21.85	99	18470	75873	110494857
Skin toxicity	107.10	21.85	48	18521	11735	110558995
Streptococcal sepsis	103.43	21.85	37	18532	5035	110565695
Nausea	102.80	21.85	444	18125	1235246	109335484
Vascular device infection	100.35	21.85	51	18518	16461	110554269
Death	97.96	21.85	298	18271	698571	109872159
Mucosal inflammation	96.88	21.85	99	18470	96042	110474688
Hepatotoxicity	96.19	21.85	82	18487	63318	110507412
Nail bed inflammation	95.80	21.85	28	18541	2002	110568728
Nasal mucosal disorder	93.41	21.85	27	18542	1856	110568874
Jaundice	92.71	21.85	78	18491	59158	110511572
Hypokalaemia	83.06	21.85	126	18443	182322	110388408
Lymphangiosis carcinomatosa	81.90	21.85	26	18543	2456	110568274
Haematotoxicity	80.73	21.85	48	18521	21034	110549696
Hyperbilirubinaemia	80.48	21.85	55	18514	30616	110540114
Pseudomonal sepsis	73.23	21.85	34	18535	9012	110561718
Asthenia	70.93	21.85	265	18304	688734	109881996
Cardiotoxicity	68.75	21.85	40	18529	16841	110553889
Varicose vein	65.40	21.85	29	18540	6911	110563819
Pleural effusion	62.22	21.85	109	18460	177600	110393130
Condition aggravated	62.02	21.85	23	18546	734813	109835917
Brain oedema	61.54	21.85	47	18522	31051	110539679
Metastasis	54.54	21.85	27	18542	8240	110562490
Rash	49.16	21.85	269	18300	820695	109750035
Weight increased	47.41	21.85	7	18562	419637	110151093
Dry skin	47.06	21.85	73	18496	107580	110463150
Metastases to spine	42.99	21.85	20	18549	5323	110565407
Botryomycosis	42.46	21.85	8	18561	79	110570651
Dermatitis acneiform	41.18	21.85	26	18543	12669	110558061
Hormone receptor positive breast cancer	41.15	21.85	11	18558	566	110570164
Onycholysis	40.92	21.85	16	18553	2783	110567947
Drug hypersensitivity	40.36	21.85	13	18556	454077	110116653
Hepatic function abnormal	39.65	21.85	61	18508	89234	110481496
Second primary malignancy	39.52	21.85	29	18540	18039	110552691
Joint swelling	38.79	21.85	13	18556	442832	110127898
Recurrent cancer	37.80	21.85	16	18553	3407	110567323
Subclavian vein thrombosis	37.25	21.85	15	18554	2817	110567913
Candida infection	37.08	21.85	43	18526	47966	110522764
Neuropathy peripheral	36.59	21.85	88	18481	179189	110391541
Transaminases	36.47	21.85	7	18562	77	110570653
Breast cancer recurrent	36.01	21.85	16	18553	3830	110566900
Eczema	35.83	21.85	52	18517	72241	110498489
Infusion related reaction	35.52	21.85	10	18559	381152	110189578
Leukonychia	34.84	21.85	7	18562	99	110570631
Tumour marker increased	34.79	21.85	17	18552	5043	110565687
Skin mass	34.10	21.85	21	18548	9795	110560935
Onychalgia	33.79	21.85	11	18558	1126	110569604
Biliary dilatation	33.68	21.85	15	18554	3610	110567120
Arthralgia	32.96	21.85	50	18519	779582	109791148
Drug interaction	32.62	21.85	22	18547	500161	110070569
Fall	32.58	21.85	32	18537	603450	109967280
Osteonecrosis of jaw	32.16	21.85	40	18529	47977	110522753
Alanine aminotransferase increased	32.07	21.85	85	18484	183688	110387042
Stomatitis	32.01	21.85	109	18460	270133	110300597
Limbal stem cell deficiency	30.85	21.85	6	18563	71	110570659
Breast cancer	30.57	21.85	35	18534	38507	110532223
Decreased appetite	30.48	21.85	159	18410	475687	110095043
Invasive ductal breast carcinoma	30.42	21.85	17	18552	6629	110564101
Central nervous system lesion	29.66	21.85	23	18546	15530	110555200
Metastatic neoplasm	29.58	21.85	16	18553	5857	110564873
Metastases to the mediastinum	29.06	21.85	9	18560	784	110569946
Erysipelas	28.51	21.85	21	18548	13137	110557593
Neoplasm progression	28.49	21.85	44	18525	64551	110506179
Intracranial pressure increased	27.88	21.85	19	18550	10516	110560214
Gastrointestinal bacterial infection	27.62	21.85	10	18559	1408	110569322
Hypertension	27.57	21.85	27	18542	510057	110060673
Abdominal pain	27.26	21.85	163	18406	512826	110057904
Restlessness	27.20	21.85	40	18529	56219	110514511
Wheezing	27.15	21.85	5	18564	255225	110315505
Pyrexia	26.92	21.85	249	18320	898016	109672714
Mobility decreased	26.70	21.85	4	18565	237418	110333312
Neurotoxicity	26.42	21.85	34	18535	42173	110528557
Performance status decreased	26.41	21.85	16	18553	7250	110563480
Off label use	26.02	21.85	147	18422	1500038	109070692
Cellulitis	25.86	21.85	62	18507	125954	110444776
HER2 positive breast cancer	25.72	21.85	7	18562	386	110570344
Discomfort	25.62	21.85	3	18566	214704	110356026
Left ventricular dysfunction	25.12	21.85	25	18544	23468	110547262
Musculoskeletal stiffness	24.86	21.85	8	18561	279814	110290916
Febrile neutropenia	24.68	21.85	112	18457	316655	110254075
Glossodynia	24.38	21.85	4	18565	222000	110348730
Lower respiratory tract infection	23.35	21.85	6	18563	243100	110327630
Brain neoplasm	23.15	21.85	14	18555	6323	110564407
Neoplasm recurrence	22.91	21.85	13	18556	5219	110565511
Product dose omission issue	22.56	21.85	13	18556	321769	110248961
Plantar erythema	22.54	21.85	6	18563	304	110570426
Pericardial effusion	22.52	21.85	37	18532	57180	110513550
Cholangitis	22.49	21.85	20	18549	16315	110554415
Metastases to chest wall	21.97	21.85	7	18562	669	110570061
Fatigue	21.86	21.85	305	18264	1215653	109355077

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EH01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors
FDA MoA	N0000175076	Protein Kinase Inhibitors
MeSH PA	D000092004	Tyrosine 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 agent
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitor

Related Drugs by ATC class:

L01EH Human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors 4 drugs

neratinib sevabertinib tucatinib zongertinib

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

Disease	Relation	SNOMED_ID
HER2-positive carcinoma of breast	indication	427685000
Torsades de pointes	contraindication	31722008
Hypokalemia	contraindication	43339004
Hepatic failure	contraindication	59927004
Interstitial pneumonia	contraindication	64667001
Left heart failure	contraindication	85232009
Prolonged QT interval	contraindication	111975006
Liver function tests abnormal	contraindication	166603001
Hypomagnesemia	contraindication	190855004
Drug-induced hepatitis	contraindication	235876009
Pregnancy, function	contraindication	289908002
Severe diarrhea	contraindication	409587002
Breastfeeding (mother)	contraindication	413712001
Congenital long QT syndrome	contraindication	442917000

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	5.62	Basic
pKa2	4.99	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Receptor tyrosine-protein kinase erbB-2	Kinase	P04626	ERBB2_HUMAN	INHIBITOR	Kd	8.15	CHEMBL	CHEMBL
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN	INHIBITOR	Kd	9.04	CHEMBL	CHEMBL
Platelet-derived growth factor receptor beta	Kinase	P09619	PGFRB_HUMAN		IC50	5.07	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		IC50	4.64	CHEMBL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	5.46	CHEMBL
Solute carrier organic anion transporter family member 1B1	Transporter	Q9Y6L6	SO1B1_HUMAN				WOMBAT-PK
Cyclin-dependent kinase 2	Kinase	P24941	CDK2_HUMAN		IC50	4.96	CHEMBL
Insulin receptor	Kinase	P06213	INSR_HUMAN	AGONIST	IC50	4.77	CHEMBL
Receptor tyrosine-protein kinase erbB-4	Kinase	Q15303	ERBB4_HUMAN		Kd	7.27	CHEMBL
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.59	CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	5.44	CHEMBL
STE20-like serine/threonine-protein kinase	Kinase	Q9H2G2	SLK_HUMAN		Kd	5.48	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 7	Kinase	O14733	MP2K7_HUMAN		Kd	5.36	CHEMBL
Receptor tyrosine-protein kinase erbB-3	Kinase	P21860	ERBB3_HUMAN		Kd	5.26	CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta	Kinase	O00750	P3C2B_HUMAN		Kd	6.17	CHEMBL
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma	Kinase	O75747	P3C2G_HUMAN		Kd	5.12	CHEMBL
Phosphatidylinositol 4-kinase beta	Kinase	Q9UBF8	PI4KB_HUMAN		Kd	6.03	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	5.96	CHEMBL
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN				WOMBAT-PK
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		EC50	5.50	CHEMBL
Tubulin alpha-1A chain	Structural		TBA1A_RAT		Kd	7.27	CHEMBL
Replicase polyprotein 1ab	Enzyme		R1AB_SARS2		Ki	4.64	CHEMBL

External reference:

ID	Source
4026029	VUID
N0000179782	NUI
D04024	KEGG_DRUG
388082-78-8	SECONDARY_CAS_RN
4026029	VANDF
C1506770	UMLSCUI
FMM	PDB_CHEM_ID
CHEMBL554	ChEMBL_ID
CHEMBL1201179	ChEMBL_ID
D000077341	MESH_DESCRIPTOR_UI
DB01259	DRUGBANK_ID
5692	IUPHAR_LIGAND_ID
8378	INN_ID
0VUA21238F	UNII
208908	PUBCHEM_CID
480167	RXNORM
339254	MMSL
d06672	MMSL
012020	NDDF
012022	NDDF
425466009	SNOMEDCT_US
425820005	SNOMEDCT_US
426238006	SNOMEDCT_US
CHEBI:192581	CHEBI
0VUA21238F	INXIGHT DRUGS

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
TYKERB	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0671	TABLET	250 mg	ORAL	NDA	34 sections
Lapatinib	HUMAN PRESCRIPTION DRUG LABEL	1	0480-3237	TABLET, FILM COATED	250 mg	ORAL	ANDA	34 sections
Lapatinib	HUMAN PRESCRIPTION DRUG LABEL	1	42291-035	TABLET, FILM COATED	250 mg	ORAL	ANDA	34 sections
Lapatinib	Human Prescription Drug Label	1	68180-801	TABLET	250 mg	ORAL	ANDA	28 sections