Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1887)
Drug Name
Neratinib
Synonyms
Neratinib; Neratinib (HKI-272); Neratinib(HKI-272); JJH94R3PWB; Nerlynx; PB-272; Q-101402; WAY-179272; HKI-272; (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide; (E)-N-(4-(3-chloro-4-(pyridin-2-ylmethoxy)phenylamino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide; 698387-09-6; C30H29ClN6O3; CHEMBL180022; HKI 272; HKI-272; UNII-JJH94R3PWB
Indication Breast cancer [ICD11: 2C60] Approved []
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 557 Topological Polar Surface Area 112
Heavy Atom Count 40 Rotatable Bond Count 11
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
9915743
PubChem SID
14886227 ; 24194959 ; 45987396 ; 76593408 ; 96025633 ; 103441767 ; 104048227 ; 104253482 ; 109693540 ; 121277958 ; 123055351 ; 124757612 ; 124950160 ; 125164416 ; 126665957 ; 126731400 ; 131477696 ; 134342020 ; 134964338 ; 135252601 ; 135727425 ; 136348728 ; 136367583 ; 136367864 ; 137006066 ; 139363252 ; 143497501 ; 144116272 ; 152186746 ; 152234948 ; 152258784 ; 152344179 ; 160647635 ; 162011383 ; 162037785 ; 162200061 ; 163883153 ; 164041890 ; 172914303 ; 174530425 ; 177748696 ; 178102313 ; 180371634 ; 185978452 ; 198962615 ; 223381071 ; 223471413 ; 223679237 ; 226878157 ; 226878158
ChEBI ID
CHEBI:61397
CAS Number
677007-74-8
TTD Drug ID
D0Q9CY
Formula
C30H29ClN6O3
Canonical SMILES
CCOC1=C(C=C2C(=C1)N=CC(=C2NC3=CC(=C(C=C3)OCC4=CC=CC=N4)Cl)C#N)NC(=O)C=CCN(C)C
InChI
1S/C30H29ClN6O3/c1-4-39-28-16-25-23(15-26(28)36-29(38)9-7-13-37(2)3)30(20(17-32)18-34-25)35-21-10-11-27(24(31)14-21)40-19-22-8-5-6-12-33-22/h5-12,14-16,18H,4,13,19H2,1-3H3,(H,34,35)(H,36,38)/b9-7+
InChIKey
JWNPDZNEKVCWMY-VQHVLOKHSA-N
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
Neratinib metabolite M10 DM002157 N. A. Oxidation - N-Demethylation 1 [2]
Neratinib metabolite M12 DM002159 N. A. Oxidation - N-Oxygenation 1 [2]
Neratinib metabolite M3 DM002158 N. A. Oxidation - O-Dealkylation 1 [2]
Neratinib metabolite M6,M7 DM002153 N. A. Conjugation - Glutathione Conjugation 1 [2]
Neratinib metabolite M8 DM002155
131634109
Oxidation - Oxygenation 1 [2]
Neratinib metabolite M4,M5 DM002156 N. A. Conjugation - Glutathione Conjugation 2 [2]
Neratinib metabolite M9,M11 DM002154 N. A. Conjugation - N-Acetylcysteine Conjugation 2 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001724 Neratinib Neratinib metabolite M6,M7 Conjugation - Glutathione Conjugation Unclear [2]
MR001725 Neratinib Neratinib metabolite M8 Oxidation - Oxygenation Unclear [2]
MR001726 Neratinib Neratinib metabolite M10 Oxidation - N-Demethylation Unclear [2]
MR001727 Neratinib Neratinib metabolite M3 Oxidation - O-Dealkylation Unclear [2]
MR001728 Neratinib Neratinib metabolite M12 Oxidation - N-Oxygenation Unclear [2]
MR001722 Neratinib metabolite M6,M7 Neratinib metabolite M9,M11 Conjugation - N-Acetylcysteine Conjugation Unclear [2]
MR001723 Neratinib metabolite M8 Neratinib metabolite M4,M5 Conjugation - Glutathione Conjugation Unclear [2]
⏷ Show the Full List of 7 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[1]
References
1 Pharmacodynamics, pharmacokinetics and clinical efficacy of neratinib in HER2-positive breast cancer and breast cancer with HER2 mutations. Expert Opin Drug Metab Toxicol. 2016 Aug;12(8):947-57.
2 Metabolic profiles of neratinib in rat by using ultra-high-performance liquid chromatography coupled with diode array detector and Q-Exactive Orbitrap tandem mass spectrometry Biomed Chromatogr. 2018 May 3:e4272. doi: 10.1002/bmc.4272.

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