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

General Information of Drug (ID: DR0881)
Drug Name
Irinotecan hydrochloride
Synonyms
Irinophore C; Irinotecan [INN:BAN]; Irinotecan lactone; Irinotecan mylan; Irinotecanum; Irinotecanum [INN-Latin]; Onivyde; irinotecan; product-irinotecan; (+)-Irinotecan; (4S)-4,11-DIETHYL-4-HYDROXY-3,14-DIOXO-3,4,12,14-TETRAHYDRO-1H-PYRANO[3',4':6,7]INDOLIZINO[1,2-B]QUINOLIN-9-YL 1,4'-BIPIPERIDINE-1'-CARBOXYLATE; 97682-44-5; AK163712; C33H38N4O6; CHEBI:80630; CHEMBL481; CP0; HSDB 7607; UNII-7673326042; IRINOTECAN, CPT-11; Camptothecin 11; Camptothecin 11 hydrochloride; Camptothecin analog; Irinotecan (hydrochloride); Irinotecan hydrochloride; Topotecin; U 101440E; 06X131E4OE; 100286-90-6; 7-Ethyl-10-(4-(1-piperidino)-1-piperidino)carbonyloxy camptothecin hydrochloride; CHEBI:5971; CPT 11; DSSTox_CID_25953; DSSTox_GSID_45953; DSSTox_RID_81249; Irinotecan hydrochloride [USAN:JAN]; MFCD01862255; NCGC00095190-01; NSC-616348; NSC616348; UNII-06X131E4OE
Indication Colon cancer [ICD11: 2B90] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 623.1 Topological Polar Surface Area 113
Heavy Atom Count 44 Rotatable Bond Count 5
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
74990
ChEBI ID
CHEBI:5971
CAS Number
100286-90-6
TTD Drug ID
D07HOB
Formula
C33H39ClN4O6
Canonical SMILES
CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)C4(CC)O)C2=NC5=C1C=C(C=C5)OC(=O)N6CCC(CC6)N7CCCCC7.Cl
InChI
1S/C33H38N4O6.ClH/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2;/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3;1H/t33-;/m0./s1
InChIKey
GURKHSYORGJETM-WAQYZQTGSA-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
7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin DM001001
10077584
Unclear 1 [8] , [9]
NPC DM001002
11756356
Unclear 1 [8] , [10] , [11]
SN-38 DM003049
104842
Unclear 1 [8] , [12] , [13]
Glucuronidated Sn-38 DM001000
54580698
Conjugation - Glucuronidation 2 [8] , [14] , [12]
NPC DM001002
11756356
Unclear 2 [8]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001224 Irinotecan hydrochloride 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin Unclear CYP3A4 ... [8], [9]
MR001225 Irinotecan hydrochloride NPC Unclear CYP3A4 [8], [10], [11]
MR001226 Irinotecan hydrochloride SN-38 Unclear CES1 ... [8], [12], [13]
MR001223 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin NPC Unclear Unclear [8]
MR001227 SN-38 Glucuronidated Sn-38 Conjugation - Glucuronidation UGT1A1 [8], [14], [12]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Beta-glucuronidase (uidA) DME1788 Escherichia coli
BGLR_ECOLI
3.2.1.31
[2]
Carboxylesterase 1 (CES1) DME0054 Homo sapiens
EST1_HUMAN
3.1.1.1
[3]
Carboxylesterase 2 (CES2) DME0057 Homo sapiens
EST2_HUMAN
3.1.1.1
[4]
Carboxylesterase 3 (CES3) DME0056 Homo sapiens
EST3_HUMAN
3.1.1.1
[4]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[7]
⏷ Show the Full List of 8  DME(s)
References
1 Irinotecan Hydrochloride was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res. 1996 Aug 15;56(16):3752-7.
3 Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23.
4 Hydrolysis of irinotecan and its oxidative metabolites, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino] carbonyloxycamptothecin and 7-ethyl-10-[4-(1-piperidino)-1-amino]-carbonyloxycamptothecin, by human carboxylesterases CES1A1, CES2, and a newly expressed carboxylesterase isoenzyme, CES3. Drug Metab Dispos. 2004 May;32(5):505-11.
5 Drugs that may have potential CYP2B6 interactions.
6 Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro. 2006 Mar;20(2):163-75.
7 Drug Interactions Flockhart Table
8 Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following I.V. infusion of [(14)C]CPT-11 in cancer patients Drug Metab Dispos. 2000 Apr;28(4):423-33.
9 Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms. Eur J Drug Metab Pharmacokinet. 2021 Mar;46(2):317-324. doi: 10.1007/s13318-021-00675-3.
10 Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93. Front Microbiol. 2023 Jan 11;13:1081094. doi: 10.3389/fmicb.2022.1081094.
11 Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen. Cancer Chemother Pharmacol. 2021 Aug;88(2):247-258. doi: 10.1007/s00280-021-04255-9.
12 Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model. Br J Pharmacol. 2023 May;180(10):1362-1378. doi: 10.1111/bph.16020.
13 UHPLC-MS/MS method for the quantification of ultra-traces of irinotecan and its metabolites in red blood cells and plasma to detect caregivers' contamination. Drug Test Anal. 2023 Jun 28. doi: 10.1002/dta.3539.
14 Transporter and metabolic enzyme-mediated intra-enteric circulation of SN-38, an active metabolite of irinotecan: A new concept. Biochem Biophys Res Commun. 2023 Jul 12;665:19-25. doi: 10.1016/j.bbrc.2023.04.109.

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