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

Stem definitionDrug idCAS RN
tyrosine kinase inhibitors 4318 850140-72-6

Description:

MoleculeDescription

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:

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

Approvals:

DateAgencyCompanyOrphan
Sept. 25, 2013 EMA
July 12, 2013 FDA BOEHRINGER INGELHEIM

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression indication 426964009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (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 strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Epidermal growth factor receptor Kinase INHIBITOR Kd 10 CHEMBL CHEMBL
Receptor tyrosine-protein kinase erbB-2 Kinase INHIBITOR Kd 8.30 CHEMBL CHEMBL
Receptor tyrosine-protein kinase erbB-4 Kinase INHIBITOR Kd 8.20 CHEMBL CHEMBL
Mitogen-activated protein kinase 9 Kinase Kd 5.68 CHEMBL
Proto-oncogene tyrosine-protein kinase Src Kinase Kd 5.55 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 2 Kinase Kd 5.74 CHEMBL
Hepatocyte growth factor receptor Kinase Kd 5.66 CHEMBL
Casein kinase I isoform epsilon Kinase Kd 5.89 CHEMBL
Receptor-interacting serine/threonine-protein kinase 2 Kinase Kd 5.57 CHEMBL
Ribosomal protein S6 kinase alpha-6 Kinase Kd 5.51 CHEMBL
Cyclin-G-associated kinase Kinase Kd 7.10 CHEMBL
Serine/threonine-protein kinase SBK1 Kinase Kd 5.32 CHEMBL
Dual specificity mitogen-activated protein kinase kinase 5 Kinase Kd 5.89 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 1 Kinase Kd 5.74 CHEMBL
Tyrosine-protein kinase FRK Kinase Kd 5.85 CHEMBL
Serine/threonine-protein kinase 10 Kinase Kd 5.37 CHEMBL
Tyrosine-protein kinase HCK Kinase Kd 5.66 CHEMBL
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform Kinase Kd 6.33 CHEMBL
Citron Rho-interacting kinase Kinase Kd 5.54 CHEMBL
Homeodomain-interacting protein kinase 4 Kinase Kd 6.44 CHEMBL
Serine/threonine-protein kinase 17A Kinase Kd 5.64 CHEMBL
Ephrin type-A receptor 6 Kinase Kd 6.47 CHEMBL
STE20-like serine/threonine-protein kinase Kinase Kd 5.43 CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2 Kinase Kd 5.80 CHEMBL
Interleukin-1 receptor-associated kinase 1 Kinase Kd 6.62 CHEMBL
Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform Kinase Kd 5.89 CHEMBL
Tyrosine-protein kinase Blk Kinase Kd 6.66 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1B Kinase Kd 5.55 CHEMBL
Receptor tyrosine-protein kinase erbB-3 Kinase Kd 5.35 CHEMBL
Ephrin type-B receptor 6 Kinase Kd 5.51 CHEMBL
Dual specificity tyrosine-phosphorylation-regulated kinase 1A Kinase Kd 6.01 CHEMBL
Tyrosine-protein kinase Lck Kinase Kd 6.24 CHEMBL
Tyrosine-protein kinase receptor UFO Kinase Kd 5.28 CHEMBL
Tyrosine-protein kinase TXK Kinase Kd 5.51 CHEMBL
Mitogen-activated protein kinase 10 Kinase Kd 5.70 CHEMBL
Mitogen-activated protein kinase 14 Kinase Kd 5.89 CHEMBL
Tyrosine-protein kinase ABL1 Kinase Kd 6.64 CHEMBL
Receptor-type tyrosine-protein kinase FLT3 Kinase Kd 5.85 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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