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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:30:31 UTC
HMDB IDHMDB14900
Secondary Accession NumbersNone
Metabolite Identification
Common NameIrinotecan
DescriptionIrinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.
Structure
Thumb
Synonyms
ValueSource
BiotecanKegg
Irinotecan hydrochloride trihydrateHMDB
Chemical FormulaC33H38N4O6
Average Molecular Weight586.678
Monoisotopic Molecular Weight586.279134968
IUPAC Name(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.0²,¹¹.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
Traditional Nameirinotecan
CAS Registry Number100286-90-6
SMILES
CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=C1C=C(OC(=O)N1CCC(CC1)N1CCCCC1)C=C2
InChI Identifier
InChI=1S/C33H38N4O6/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/t33-/m0/s1
InChI KeyInChIKey=UWKQSNNFCGGAFS-XIFFEERXSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassCamptothecins
Sub ClassNot Available
Direct ParentCamptothecins
Alternative Parents
Substituents
  • Camptothecin
  • Hydroxyquinoline
  • Quinoline
  • Pyranopyridine
  • Piperidinecarboxylic acid
  • Pyridinone
  • 4-aminopiperidine
  • Benzenoid
  • Pyridine
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Tertiary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Lactone
  • Lactam
  • Carboxylic acid ester
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Parasympathomimetics
  • Prodrugs
  • Radiation-Sensitizing Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point222 - 223 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.07e-01 g/LNot Available
LogP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.11 mg/mLALOGPS
logP3.94ALOGPS
logP2.78ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)11.71ChemAxon
pKa (Strongest Basic)9.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area112.51 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity161.33 m3·mol-1ChemAxon
Polarizability65.27 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB LinkKEGG Link
Irinotecan Metabolism PathwaySMP00600Not Available
Irinotecan PathwaySMP00433Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00762
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00762
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00762
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID54825
KEGG Compound IDC16641
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIrinotecan
NuGOwiki LinkHMDB14900
Metagene LinkHMDB14900
METLIN IDNot Available
PubChem Compound60838
PDB IDCP0
ChEBI ID105985
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. [9342501 ]
  2. Ramesh M, Ahlawat P, Srinivas NR: 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. [19852077 ]
  3. Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. [15007088 ]
  4. O'Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. [17008691 ]
  5. FDA label

Enzymes

General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate. Is also able to catalyze the glucuronidation of 17beta-estradiol, 17alpha-ethinylestradiol, 1-hydroxypyrene, 4-methylumbelliferone, 1-naphthol, paranitrophenol, scopoletin, and umbelliferone.
Gene Name:
UGT1A1
Uniprot ID:
P22309
Molecular weight:
59590.91
References
  1. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. [9726089 ]
General function:
Involved in transferase activity, transferring hexosyl groups
Specific function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:
UGT1A9
Uniprot ID:
O60656
Molecular weight:
59940.495
References
  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. [9342501 ]
General function:
Lipid transport and metabolism
Specific function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acyl-CoA ester. Hydrolyzes the methyl ester group of cocaine to form benzoylecgonine. Catalyzes the transesterification of cocaine to form cocaethylene. Displays fatty acid ethyl ester synthase activity, catalyzing the ethyl esterification of oleic acid to ethyloleate.
Gene Name:
CES1
Uniprot ID:
P23141
Molecular weight:
62520.62
Reactions
Irinotecan + Water → SN-38 + 1,4'-Bipiperidine-1'-carboxylic aciddetails
References
  1. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. [9342501 ]
  2. Ramesh M, Ahlawat P, Srinivas NR: 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. [19852077 ]
  3. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. [9726089 ]
General function:
Lipid transport and metabolism
Specific function:
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine.
Gene Name:
CES2
Uniprot ID:
O00748
Molecular weight:
68898.39
Reactions
Irinotecan + Water → SN-38 + 1,4'-Bipiperidine-1'-carboxylic aciddetails
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Ramesh M, Ahlawat P, Srinivas NR: 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. [19852077 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
  3. Kuhn JG: Pharmacology of irinotecan. Oncology (Williston Park). 1998 Aug;12(8 Suppl 6):39-42. [9726089 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular weight:
57108.065
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular weight:
57525.03
General function:
Involved in DNA binding
Specific function:
Relieves DNA strain that arise during duplication of mitochondrial DNA
Gene Name:
TOP1MT
Uniprot ID:
Q969P6
Molecular weight:
69871.4
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Yoshikawa M, Ikegami Y, Hayasaka S, Ishii K, Ito A, Sano K, Suzuki T, Togawa T, Yoshida H, Soda H, Oka M, Kohno S, Sawada S, Ishikawa T, Tanabe S: Novel camptothecin analogues that circumvent ABCG2-associated drug resistance in human tumor cells. Int J Cancer. 2004 Jul 20;110(6):921-7. [15170677 ]
  4. Yoshikawa M, Ikegami Y, Sano K, Yoshida H, Mitomo H, Sawada S, Ishikawa T: Transport of SN-38 by the wild type of human ABC transporter ABCG2 and its inhibition by quercetin, a natural flavonoid. J Exp Ther Oncol. 2004 Apr;4(1):25-35. [15255290 ]
  5. Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S: Novel agents that potentially inhibit irinotecan-induced diarrhea. Curr Med Chem. 2005;12(11):1343-58. [15975002 ]
  6. Nakagawa H, Saito H, Ikegami Y, Aida-Hyugaji S, Sawada S, Ishikawa T: Molecular modeling of new camptothecin analogues to circumvent ABCG2-mediated drug resistance in cancer. Cancer Lett. 2006 Mar 8;234(1):81-9. Epub 2005 Nov 23. [16309825 ]
  7. Ishikawa T, Ikegami Y, Sano K, Nakagawa H, Sawada S: Transport mechanism-based drug molecular design: novel camptothecin analogues to circumvent ABCG2-associated drug resistance of human tumor cells. Curr Pharm Des. 2006;12(3):313-25. [16454746 ]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  9. Ramesh M, Ahlawat P, Srinivas NR: 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. [19852077 ]
  10. Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. [9342501 ]

Transporters

General function:
Involved in transporter activity
Specific function:
Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver
Gene Name:
SLCO1B1
Uniprot ID:
Q9Y6L6
Molecular weight:
76448.0
References
  1. Nozawa T, Minami H, Sugiura S, Tsuji A, Tamai I: Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos. 2005 Mar;33(3):434-9. Epub 2004 Dec 17. [15608127 ]
General function:
Involved in ATP binding
Specific function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular weight:
171589.5
References
  1. Chen ZS, Furukawa T, Sumizawa T, Ono K, Ueda K, Seto K, Akiyama SI: ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P. Mol Pharmacol. 1999 May;55(5):921-8. [10220571 ]
General function:
Involved in ATP binding
Specific function:
Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
References
  1. Wang X, Furukawa T, Nitanda T, Okamoto M, Sugimoto Y, Akiyama S, Baba M: Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72. [12488537 ]
  2. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH: Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001 Apr;7(4):935-41. [11309344 ]
General function:
Involved in transmembrane transport
Specific function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular weight:
61279.5
References
  1. Shnitsar V, Eckardt R, Gupta S, Grottker J, Muller GA, Koepsell H, Burckhardt G, Hagos Y: Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine. Cancer Res. 2009 Feb 15;69(4):1494-501. Epub 2009 Feb 3. [19190342 ]