Scroll

afatinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	4318	850140-72-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: afatinib tovok afatinib dimaleate gilotrif BIBW2992 afatinib maleate	A quinazoline and butenamide derivative that acts as a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER. Molecular weight: 485.94 Formula: C24H25ClFN5O3 CLOGP: 4.34 LIPINSKI: 0 HAC: 8 HDO: 2 TPSA: 88.61 ALOGS: -4.58 ROTB: 8 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

afatinib
tovok
afatinib dimaleate
gilotrif
BIBW2992
afatinib maleate

A quinazoline and butenamide derivative that acts as a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER.

Molecular weight: 485.94
Formula: C24H25ClFN5O3
CLOGP: 4.34
LIPINSKI: 0
HAC: 8
HDO: 2
TPSA: 88.61
ALOGS: -4.58
ROTB: 8

Status: ONP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Hosey CM, Chan R, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Sept. 25, 2013	EMA
July 12, 2013	FDA	BOEHRINGER INGELHEIM

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
Malignant neoplasm progression	1640.57	26.81	554	7452	64372	46613684
Diarrhoea	1166.95	26.81	863	7143	558739	46119317
Paronychia	704.24	26.81	162	7844	4404	46673652
Stomatitis	353.13	26.81	190	7816	68107	46609949
Metastases to central nervous system	266.22	26.81	92	7914	11129	46666927
Rash	251.75	26.81	306	7700	356206	46321850
Dermatitis acneiform	203.70	26.81	59	7947	4011	46674045
Decreased appetite	181.33	26.81	193	7813	193643	46484413
EGFR gene mutation	145.75	26.81	25	7981	133	46677923
Skin toxicity	131.15	26.81	41	7965	3613	46674443
Metastases to meninges	123.95	26.81	34	7972	1893	46676163
Dehydration	121.70	26.81	143	7863	159397	46518659
Acne	93.15	26.81	52	7954	19867	46658189
Dry skin	86.78	26.81	65	7941	40951	46637105
Non-small cell lung cancer	67.67	26.81	24	7982	3120	46674936
Nail disorder	67.47	26.81	31	7975	7865	46670191
Pleural effusion	60.83	26.81	73	7933	82879	46595177
Skin fissures	58.95	26.81	28	7978	7652	46670404
Mucosal inflammation	57.42	26.81	50	7956	38926	46639130
Skin disorder	55.53	26.81	39	7967	22224	46655832
Metastases to bone	54.08	26.81	35	7971	17441	46660615
Vomiting	53.11	26.81	184	7822	452610	46225446
Drug resistance	49.40	26.81	33	7973	17335	46660721
Metastases to lung	44.81	26.81	26	7980	10670	46667386
Cutaneous symptom	43.81	26.81	9	7997	140	46677916
Interstitial lung disease	42.04	26.81	49	7957	53900	46624156
Metastases to liver	41.30	26.81	31	7975	19554	46658502
Arthralgia	38.26	26.81	8	7998	364595	46313461
Gene mutation	38.25	26.81	12	7994	1068	46676988
Onychoclasis	37.19	26.81	18	7988	5126	46672930
Neoplasm progression	34.86	26.81	32	7974	26651	46651405
Small cell lung cancer	34.00	26.81	12	7994	1537	46676519
Acquired gene mutation	31.12	26.81	9	7997	607	46677449
Oral pain	30.97	26.81	29	7977	24768	46653288
Rash pustular	29.44	26.81	17	7989	6912	46671144
Pneumonitis	29.43	26.81	30	7976	28390	46649666
Epistaxis	27.98	26.81	44	7962	64261	46613795
Prerenal failure	27.29	26.81	10	7996	1427	46676629

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
Malignant neoplasm progression	1191.94	34.62	420	3619	71867	29876572
Diarrhoea	555.37	34.62	409	3630	333694	29614745
Paronychia	343.87	34.62	80	3959	2931	29945508
Rash	247.11	34.62	204	3835	191685	29756754
Metastases to central nervous system	243.14	34.62	73	3966	7211	29941228
Stomatitis	214.28	34.62	103	3936	37176	29911263
EGFR gene mutation	140.81	34.62	22	4017	78	29948361
Dermatitis acneiform	103.47	34.62	36	4003	5653	29942786
Interstitial lung disease	85.10	34.62	68	3971	60129	29888310
Decreased appetite	76.08	34.62	97	3942	149813	29798626
Acne	53.80	34.62	26	4013	9410	29939029
Skin toxicity	53.11	34.62	19	4020	3230	29945209
Dehydration	44.63	34.62	68	3971	123471	29824968
Metastases to bone	44.40	34.62	23	4016	9635	29938804
Lymphangiosis carcinomatosa	43.15	34.62	12	4027	897	29947542
Metastases to meninges	39.86	34.62	12	4027	1187	29947252
Pleural effusion	37.52	34.62	48	3991	74018	29874421
Nail disorder	35.30	34.62	12	4027	1753	29946686

Pharmacologic Action:

Source	Code	Description
ATC	L01EB03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
FDA MoA	N0000175076	Protein Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:38637	tyrosine kinase inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression	indication	426964009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.1	acidic
pKa2	8.94	Basic
pKa3	4.09	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 20MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2021	TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR RECEPTOR MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
EQ 30MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2021	TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR RECEPTOR MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2021	TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR RECEPTOR MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
EQ 20MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	April 15, 2023	TREATMENT OF PATIENTS WITH METASTATIC, SQUAMOUS, NON-SMALL CELL LUNG CANCER PROGRESSING AFTER PLATINUM-BASED CHEMOTHERAPY
EQ 30MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	April 15, 2023	TREATMENT OF PATIENTS WITH METASTATIC, SQUAMOUS, NON-SMALL CELL LUNG CANCER PROGRESSING AFTER PLATINUM-BASED CHEMOTHERAPY
EQ 40MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	April 15, 2023	TREATMENT OF PATIENTS WITH METASTATIC, SQUAMOUS, NON-SMALL CELL LUNG CANCER PROGRESSING AFTER PLATINUM-BASED CHEMOTHERAPY
EQ 20MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2025	FIRST-LINE TREATMENT OF METASTATIC NONSMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR MUTATIONS OTHER THAN EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
EQ 30MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2025	FIRST-LINE TREATMENT OF METASTATIC NONSMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR MUTATIONS OTHER THAN EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
EQ 40MG BASE	GILOTRIF	BOEHRINGER INGELHEIM	N201292	July 12, 2013	RX	TABLET	ORAL	Jan. 12, 2025	FIRST-LINE TREATMENT OF METASTATIC NONSMALL CELL LUNG CANCER WHOSE TUMORS HAVE NON-RESISTANT EPIDERMAL GROWTH FACTOR MUTATIONS OTHER THAN EXON 19 DELETIONS OR EXON 21 (L858R) SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN	INHIBITOR	Kd	10	CHEMBL	CHEMBL
Receptor tyrosine-protein kinase erbB-2	Kinase	P04626	ERBB2_HUMAN	INHIBITOR	Kd	8.30	CHEMBL	CHEMBL
Receptor tyrosine-protein kinase erbB-4	Kinase	Q15303	ERBB4_HUMAN	INHIBITOR	Kd	8.20	CHEMBL	CHEMBL
Mitogen-activated protein kinase 9	Kinase	P45984	MK09_HUMAN		Kd	5.68	CHEMBL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		Kd	5.55	CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 2	Kinase	Q92630	DYRK2_HUMAN		Kd	5.74	CHEMBL
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN		Kd	5.66	CHEMBL
Casein kinase I isoform epsilon	Kinase	P49674	KC1E_HUMAN		Kd	5.89	CHEMBL
Receptor-interacting serine/threonine-protein kinase 2	Kinase	O43353	RIPK2_HUMAN		Kd	5.57	CHEMBL
Ribosomal protein S6 kinase alpha-6	Kinase	Q9UK32	KS6A6_HUMAN		Kd	5.51	CHEMBL
Cyclin-G-associated kinase	Kinase	O14976	GAK_HUMAN		Kd	7.10	CHEMBL
Serine/threonine-protein kinase SBK1	Kinase	Q52WX2	SBK1_HUMAN		Kd	5.32	CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5	Kinase	Q13163	MP2K5_HUMAN		Kd	5.89	CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1	Kinase	Q9BUB5	MKNK1_HUMAN		Kd	5.74	CHEMBL
Tyrosine-protein kinase FRK	Kinase	P42685	FRK_HUMAN		Kd	5.85	CHEMBL
Serine/threonine-protein kinase 10	Kinase	O94804	STK10_HUMAN		Kd	5.37	CHEMBL
Tyrosine-protein kinase HCK	Kinase	P08631	HCK_HUMAN		Kd	5.66	CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform	Kinase	P15735	PHKG2_HUMAN		Kd	6.33	CHEMBL
Citron Rho-interacting kinase	Kinase	O14578	CTRO_HUMAN		Kd	5.54	CHEMBL
Homeodomain-interacting protein kinase 4	Kinase	Q8NE63	HIPK4_HUMAN		Kd	6.44	CHEMBL
Serine/threonine-protein kinase 17A	Kinase	Q9UEE5	ST17A_HUMAN		Kd	5.64	CHEMBL
Ephrin type-A receptor 6	Kinase	Q9UF33	EPHA6_HUMAN		Kd	6.47	CHEMBL
STE20-like serine/threonine-protein kinase	Kinase	Q9H2G2	SLK_HUMAN		Kd	5.43	CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2	Kinase	Q9HBH9	MKNK2_HUMAN		Kd	5.80	CHEMBL
Interleukin-1 receptor-associated kinase 1	Kinase	P51617	IRAK1_HUMAN		Kd	6.62	CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform	Kinase	Q16816	PHKG1_HUMAN		Kd	5.89	CHEMBL
Tyrosine-protein kinase Blk	Kinase	P51451	BLK_HUMAN		Kd	6.66	CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1B	Kinase	Q9Y463	DYR1B_HUMAN		Kd	5.55	CHEMBL
Receptor tyrosine-protein kinase erbB-3	Kinase	P21860	ERBB3_HUMAN		Kd	5.35	CHEMBL
Ephrin type-B receptor 6	Kinase	O15197	EPHB6_HUMAN		Kd	5.51	CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1A	Kinase	Q13627	DYR1A_HUMAN		Kd	6.01	CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		Kd	6.24	CHEMBL
Tyrosine-protein kinase receptor UFO	Kinase	P30530	UFO_HUMAN		Kd	5.28	CHEMBL
Tyrosine-protein kinase TXK	Kinase	P42681	TXK_HUMAN		Kd	5.51	CHEMBL
Mitogen-activated protein kinase 10	Kinase	P53779	MK10_HUMAN		Kd	5.70	CHEMBL
Mitogen-activated protein kinase 14	Kinase	Q16539	MK14_HUMAN		Kd	5.89	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		Kd	6.64	CHEMBL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN		Kd	5.85	CHEMBL

External reference:

ID	Source
41UD74L59M	UNII
4032662	VUID
N0000188388	NUI
D09724	KEGG_DRUG
850140-73-7	SECONDARY_CAS_RN
4032662	VANDF
4032663	VANDF
C2987648	UMLSCUI
CHEBI:61390	CHEBI
0WM	PDB_CHEM_ID
CHEMBL1173655	ChEMBL_ID
CHEMBL2105712	ChEMBL_ID
10184653	PUBCHEM_CID
CHEMBL2347958	ChEMBL_ID
DB08916	DRUGBANK_ID
D000077716	MESH_DESCRIPTOR_UI
9230	INN_ID
5667	IUPHAR_LIGAND_ID
1430268	RXNORM
204142	MMSL
29566	MMSL
d08113	MMSL
015117	NDDF
015118	NDDF
703579002	SNOMEDCT_US
703580004	SNOMEDCT_US
703582007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Gilotrif	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0137	TABLET, FILM COATED	30 mg	ORAL	NDA	31 sections
Gilotrif	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0138	TABLET, FILM COATED	40 mg	ORAL	NDA	31 sections
Gilotrif	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0141	TABLET, FILM COATED	20 mg	ORAL	NDA	31 sections