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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2013-05-17 01:25:13 UTC
Update Date2019-07-23 07:14:28 UTC
HMDB IDHMDB0060499
Secondary Accession Numbers
  • HMDB60499
Metabolite Identification
Common NameNPC
DescriptionNPC is a metabolite of irinotecan. Irinotecan is a drug used for the treatment of cancer. Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin. Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. This includes the regimen FOLFIRI, which consists of infusional 5-fluorouracil, leucovorin, and irinotecan. Irinotecan received accelerated approval by the U.S. (Wikipedia ) Irinotecan is subjected to be shunted between CYP3A4 mediated oxidative metabolism to form two inactive metabolites APC or NPC and tissue carboxylesterase mediated hydrolysis to form SN-38 which is eventually detoxified via glucuronidation by UGT1A1 to form SN-38G. (PMID: 12570720 ) The active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxycamptothecin (SN-38), is either formed through enzymatic cleavage of CPT-11 by carboxyl esterases (CEs) or through cytochrome P-450 3A-mediated oxidation to 7-ethyl-10-[4-(1-piperidino)-1-amino] carbonyloxycamptothecin (NPC) and a subsequent conversion by CE. (PMID: 10999728 )
Structure
Data?1563866068
SynonymsNot Available
Chemical FormulaC28H30N4O6
Average Molecular Weight518.561
Monoisotopic Molecular Weight518.216534712
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(11),3,5,7,9,15(20)-heptaen-7-yl 4-aminopiperidine-1-carboxylate
Traditional NameNPC
CAS Registry NumberNot Available
SMILES
CCC1=C2C=C(OC(=O)N3CCC(N)CC3)C=CC2=NC2=C1CN1C2=CC2=C(COC(=O)[C@]2(O)CC)C1=O
InChI Identifier
InChI=1S/C28H30N4O6/c1-3-17-18-11-16(38-27(35)31-9-7-15(29)8-10-31)5-6-22(18)30-24-19(17)13-32-23(24)12-21-20(25(32)33)14-37-26(34)28(21,36)4-2/h5-6,11-12,15,36H,3-4,7-10,13-14,29H2,1-2H3/t28-/m0/s1
InChI KeyAPWFTHDYKJHNEV-NDEPHWFRSA-N
Chemical Taxonomy
Description 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
  • Pyranopyridine
  • Quinoline
  • Piperidinecarboxylic acid
  • 4-aminopiperidine
  • Pyridinone
  • Piperidine
  • Pyridine
  • Benzenoid
  • Carbamic acid ester
  • Tertiary alcohol
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Lactam
  • Lactone
  • Carbonic acid derivative
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Primary aliphatic amine
  • Organooxygen compound
  • Organopnictogen compound
  • Alcohol
  • Primary amine
  • Carbonyl group
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic oxide
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Physical Properties
StateNot Available
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.17 g/LALOGPS
logP2.4ALOGPS
logP0.99ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)11.72ChemAxon
pKa (Strongest Basic)9.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area135.29 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity139.12 m³·mol⁻¹ChemAxon
Polarizability56.6 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Collision Cross Sections

NameAdductTypeData SourceValueReference
DarkChem[M+H]+PredictedNot Available217.77631661259
DarkChem[M-H]-PredictedNot Available216.72431661259

Retention Indices

Underivatized

Not Available

Derivatized

DerivativeValueReference
NPC,1TMS,#14523.3115https://arxiv.org/abs/1905.12712
NPC,1TMS,#24626.0293https://arxiv.org/abs/1905.12712
NPC,1TBDMS,#14714.549https://arxiv.org/abs/1905.12712
NPC,1TBDMS,#24838.1875https://arxiv.org/abs/1905.12712
Spectra

GC-MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-3001900000-8c258c33503227186d902017-09-20View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-020s-7100190000-57a04835b3260d62318f2017-10-06View Spectrum
MSMass Spectrum (Electron Ionization)splash10-0002-3001900000-8c258c33503227186d902021-09-05View Spectrum

LC-MS/MS

Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0uxr-1601190000-f7732258181788a4f6a62017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fc0-4914410000-8e809aa535ad79d205532017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zgi-9400000000-63746df667fed14115e32017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-1401590000-893de4cd7001406d84a42017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00vm-3906840000-17ebfe5e43ffd714d8c82017-10-06View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002e-9725100000-daa9ad1f7a2a7c152ce22017-10-06View Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Kidney
  • Liver
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableNormal
      Not Available
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDC16543
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNPC
METLIN IDNot Available
PubChem Compound11756356
PDB IDNot Available
ChEBI IDNot Available
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Magrane M: UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford). 2011 Mar 29;2011:bar009. doi: 10.1093/database/bar009. Print 2011. [PubMed:21447597 ]
  2. Ma MK, McLeod HL: Lessons learned from the irinotecan metabolic pathway. Curr Med Chem. 2003 Jan;10(1):41-9. [PubMed:12570720 ]
  3. Kehrer DF, Yamamoto W, Verweij J, de Jonge MJ, de Bruijn P, Sparreboom A: Factors involved in prolongation of the terminal disposition phase of SN-38: clinical and experimental studies. Clin Cancer Res. 2000 Sep;6(9):3451-8. [PubMed:10999728 ]

Enzymes

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
NPC + Water → SN-38 + 4-Amino-1-piperidinecarboxylic aciddetails
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
NPC + Water → SN-38 + 4-Amino-1-piperidinecarboxylic aciddetails