Details of the Drug

General Information of Drug (ID: DMTKD7Q)

Drug Name
BIBW 2992
Synonyms
Afatinib; Tomtovok; Tovok; BIBW-2992; Tovok (TN); Tovok, BIBW2992; (2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-tetrahydrofuran-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide; EGFR inhibitor 2nd gens
Indication
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Approved [1], [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 485.9
Topological Polar Surface Area (xlogp) 3.6
Rotatable Bond Count (rotbonds) 8
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-5 h [3]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
Clearance
The total body clearance of drug is 1530 mL/min [5]
Elimination
Following administration of an oral solution of 15 mg afatinib, 85.4% of the dose was recovered in the feces and 4.3% in urine [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 37 hours [3]
Metabolism
The drug is metabolized via the enzyme-catalyzed metabolic reactions [3]
Vd
The volume of distribution (Vd) of drug is 4500 L [5]
Chemical Identifiers
Formula
C24H25ClFN5O3
IUPAC Name
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-[(3S)-oxolan-3-yl]oxyquinazolin-6-yl]-4-(dimethylamino)but-2-enamide
Canonical SMILES
CN(C)C/C=C/C(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)O[C@H]4CCOC4
InChI
InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1
InChIKey
ULXXDDBFHOBEHA-CWDCEQMOSA-N
Cross-matching ID
PubChem CID
10184653
ChEBI ID
CHEBI:61390
CAS Number
850140-72-6
DrugBank ID
DB08916
TTD ID
D05UFG
VARIDT ID
DR00354

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [6]
Erbb2 tyrosine kinase receptor (HER2) TT6EO5L ERBB2_HUMAN Inhibitor [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Epidermal growth factor receptor (EGFR) DTT EGFR 5.84E-05 0.32 0.55
P-glycoprotein 1 (ABCB1) DTP P-GP 1.42E-02 -2.10E-01 -5.11E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 1.07E-06 -3.94E-01 -6.94E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as BIBW 2992
DDI Drug Name DDI Drug ID Severity Mechanism Disease REF
PF-06463922 DMKM7EW Moderate Accelerated clearance of BIBW 2992 due to the transporter induction by PF-06463922. Lung cancer [2C25] [40]
Coadministration of a Drug Treating the Disease Different from BIBW 2992 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of BIBW 2992 and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [41]
Arn-509 DMT81LZ Moderate Accelerated clearance of BIBW 2992 due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [40]
Ag-221 DMS0ZBI Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [41]
Erdafitinib DMI782S Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [42]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of BIBW 2992 and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [43]
Talazoparib DM1KS78 Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Talazoparib. Breast cancer [2C60-2C6Y] [44]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of BIBW 2992 and Cannabidiol. Epileptic encephalopathy [8A62] [45]
Ripretinib DM958QB Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Ripretinib. Gastrointestinal stromal tumour [2B5B] [41]
Fostemsavir DM50ILT Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Fostemsavir. Human immunodeficiency virus disease [1C60-1C62] [46]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of BIBW 2992 and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [47]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of BIBW 2992 and Idelalisib. Mature B-cell leukaemia [2A82] [48]
Ibrutinib DMHZCPO Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Ibrutinib. Mature B-cell lymphoma [2A85] [45]
Arry-162 DM1P6FR Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Arry-162. Melanoma [2C30] [41]
Ubrogepant DM749I3 Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Ubrogepant. Migraine [8A80] [49]
Rimegepant DMHOAUG Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Rimegepant. Migraine [8A80] [50]
Lasmiditan DMXLVDT Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Lasmiditan. Migraine [8A80] [51]
Rucaparib DM9PVX8 Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Rucaparib. Ovarian cancer [2C73] [52]
Darolutamide DMV7YFT Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [53]
Tedizolid DMG2SKR Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [45]
Pitolisant DM8RFNJ Moderate Increased metabolism of BIBW 2992 caused by Pitolisant mediated induction of UGT. Somnolence [MG42] [45]
Fostamatinib DM6AUHV Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [54]
Lusutrombopag DMH6IKO Moderate Decreased clearance of BIBW 2992 due to the transporter inhibition by Lusutrombopag. Thrombocytopenia [3B64] [52]
⏷ Show the Full List of 22 DDI Information of This Drug

References

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48 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
49 Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
50 Product Information. Nurtec ODT (rimegepant). Biohaven Pharmaceuticals, New Haven, CT.
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