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

General Information of Drug (ID: DR0858)
Drug Name
Imatinib mesylate
Synonyms
Imatinib; Imatinib (STI571); Imatinib Methansulfonate; Imatinib [INN:BAN]; Imatinib free base; Imatinib(STI571); Gleevec; Glivec; Imatinib (mesylate); Imatinib Mesylate (STI571); Imatinib mesilate; Imatinib mesylate; Imatinib mesylate (USAN); Imatinib mesylate, 98%; Imatinib, methanesulfonate salt; ST-1571 Mesylate; imatinib methanesulfonate; imatinib monomesylate; 220127-57-1; 4-[(4-Methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]phenyl]-benzamide monomethanesulfonate; 8A1O1M485B; AK-44930; CGP-57148B; CHEBI:31690; HSDB 7142; NSC-716051; UNII-8A1O1M485B; STI571; 152459-95-5; 4-(4-METHYL-PIPERAZIN-1-YLMETHYL)-N-[4-METHYL-3-(4-PYRIDIN-3-YL-PYRIMIDIN-2-YLAMINO)-PHENYL]-BENZAMIDE; CCRIS 9076; CGP-57148; CHEMBL941; Cgp 57148; N-(4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide; BKJ8M8G5HI; UNII-BKJ8M8G5HI
Indication Chronic myelogenous leukaemia [ICD11: 2A20] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 589.7 Topological Polar Surface Area 149
Heavy Atom Count 42 Rotatable Bond Count 7
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 10
Cross-matching ID
PubChem CID
123596
ChEBI ID
CHEBI:31690
CAS Number
220127-57-1
TTD Drug ID
D0AZ3C
Formula
C30H35N7O4S
Canonical SMILES
CC1=C(C=C(C=C1)NC(=O)C2=CC=C(C=C2)CN3CCN(CC3)C)NC4=NC=CC(=N4)C5=CN=CC=C5.CS(=O)(=O)O
InChI
1S/C29H31N7O.CH4O3S/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36;1-5(2,3)4/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34);1H3,(H,2,3,4)
InChIKey
YLMAHDNUQAMNNX-UHFFFAOYSA-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
AFN911 DM004310
131750717
Oxidation - Benzyl hydroxylation 1 [4]
APG049 imatinib DM004317 N. A. Oxidation - Oxidationn 1 [12]
APG050 imatinib DM004316 N. A. Oxidation - Oxidationn 1 [12]
Deaminated imatinib DM004307
53167
Multi-steps Reaction - Oxidationn deamination; carboxylation 1 [12]
M28.8 imatinib DM004315 N. A. Oxidation - Oxidationn 1 [12]
M29.6 imatinib DM004314 N. A. Oxidation - Oxidationn 1 [12]
M7 N-oxidation imatinib DM004313 N. A. Oxidation - N-oxidation 1 [4]
N-Desmethylimatinib DM004309
9869737
Oxidation - N-demethylation 1 [2] , [3] , [4]
Piperidine N-oxide imatinib DM004311 N. A. Oxidation - N-4 oxidation 1 [4]
Pyridine N-oxide imatinib DM004312
9827642
Oxidation - N-oxidation 1 [4]
M42.2 imatinib DM004308
68495594
Multi-steps Reaction - Oxidationn deamination; carboxylation 2 [12]
⏷ Show the Full List of 11  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR004667 Imatinib mesylate Deaminated imatinib Multi-steps Reaction - Oxidationn deamination; carboxylation Unclear [12]
MR004668 Imatinib mesylate M42.2 imatinib Multi-steps Reaction - Oxidationn deamination; carboxylation Unclear [12]
MR004669 Imatinib mesylate N-Desmethylimatinib Oxidation - N-demethylation CYP2C9 ... [2], [3], [4]
MR004670 Imatinib mesylate AFN911 Oxidation - Benzyl hydroxylation CYP3A4 ... [4]
MR004671 Imatinib mesylate Piperidine N-oxide imatinib Oxidation - N-4 oxidation FMO3 ... [4]
MR004672 Imatinib mesylate Pyridine N-oxide imatinib Oxidation - N-oxidation FMO3 ... [4]
MR004673 Imatinib mesylate M7 N-oxidation imatinib Oxidation - N-oxidation CYP1A1 ... [4]
MR004674 Imatinib mesylate M29.6 imatinib Oxidation - Oxidationn Unclear [12]
MR004675 Imatinib mesylate M28.8 imatinib Oxidation - Oxidationn Unclear [12]
MR004676 Imatinib mesylate APG050 imatinib Oxidation - Oxidationn Unclear [12]
MR004677 Imatinib mesylate APG049 imatinib Oxidation - Oxidationn Unclear [12]
⏷ Show the Full List of 11 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2] , [3] , [4]
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[5]
Cytochrome P450 1B1 (CYP1B1) DME0023 Homo sapiens
CP1B1_HUMAN
1.14.14.1
[2] , [3] , [4]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[6]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[7]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[8]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[9]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[10]
Cytochrome P450 4F2 (CYP4F2) DME0025 Homo sapiens
CP4F2_HUMAN
1.14.13.30
[2] , [3] , [4]
Dimethylaniline oxidase 3 (FMO3) DME0039 Homo sapiens
FMO3_HUMAN
1.14.13.8
[4]
Leukotriene B4 omega-hydroxylase (CYP4F3) DME0034 Homo sapiens
CP4F3_HUMAN
1.14.14.1
[2] , [3] , [4]
Prostaglandin G/H synthase 1 (COX-1) DME0091 Homo sapiens
PGH1_HUMAN
1.14.99.1
[2]
Unclear metabolic mechanism (DME-unclear) DME1360 Anaerostipes hadrus Not Available Not Available [11]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [11]
⏷ Show the Full List of 15  DME(s)
References
1 Imatinib Mesylate was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
3 Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes
4 In vitro biotransformation of imatinib by the tumor expressed CYP1A1 and CYP1B1
5 The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
6 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
7 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
8 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
9 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
10 Drug Interactions Flockhart Table
11 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
12 Metabolism and disposition of imatinib mesylate in healthy volunteers

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