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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2020-02-26 21:39:56 UTC
HMDB IDHMDB0014584
Secondary Accession Numbers
  • HMDB14584
Metabolite Identification
Common NameGemcitabine
DescriptionGemcitabine, also known as dfdcyd or 2',2'-DFDC, belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. Pyrimidine 2'-deoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2. Gemcitabine is a drug. Gemcitabine is an extremely weak basic (essentially neutral) compound (based on its pKa). Within humans, gemcitabine participates in a number of enzymatic reactions. In particular, gemcitabine can be biosynthesized from gemcitabine monophosphate through its interaction with the enzyme 5'(3')-deoxyribonucleotidase, cytosolic type. In addition, gemcitabine can be converted into gemcitabine monophosphate through its interaction with the enzyme deoxycytidine kinase. In humans, gemcitabine is involved in gemcitabine action pathway.
Structure
Data?1582753196
Synonyms
ValueSource
2',2'-DifluorodeoxycytidineChEBI
2'-Deoxy-2',2'-difluorocytidineChEBI
4-Amino-1-((2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-oneChEBI
GemcitabinaChEBI
GemcitabinumChEBI
DFdCydHMDB
2',2'-Difluoro-2'-deoxycytidineHMDB
2'-Deoxy-2'-difluorocytidineHMDB
Gemcitabine, (D-threo-pentafuranosyl)-isomerHMDB
Gemcitabine, (alpha-D-threo-pentofuranosyl)-isomerHMDB
2'-Deoxy-2',2''-difluorocytidine-5'-O-monophosphateHMDB
Gemcitabine hydrochlorideHMDB
2',2'-DFDCHMDB
GemzarHMDB
Gemcitabine, (beta-D-threo-pentafuranosyl)-isomerHMDB
Chemical FormulaC9H11F2N3O4
Average Molecular Weight263.1981
Monoisotopic Molecular Weight263.071762265
IUPAC Name4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
Traditional Namegemcitabine
CAS Registry Number95058-81-4
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F
InChI Identifier
InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1
InChI KeySDUQYLNIPVEERB-QPPQHZFASA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. Pyrimidine 2'-deoxyribonucleosides are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassPyrimidine nucleosides
Sub ClassPyrimidine 2'-deoxyribonucleosides
Direct ParentPyrimidine 2'-deoxyribonucleosides
Alternative Parents
Substituents
  • Pyrimidine 2'-deoxyribonucleoside
  • Aminopyrimidine
  • Pyrimidone
  • Hydropyrimidine
  • Pyrimidine
  • Imidolactam
  • Heteroaromatic compound
  • Tetrahydrofuran
  • Fluorohydrin
  • Halohydrin
  • Secondary alcohol
  • Organoheterocyclic compound
  • Azacycle
  • Oxacycle
  • Alkyl halide
  • Organopnictogen compound
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Organic oxygen compound
  • Alkyl fluoride
  • Alcohol
  • Organic nitrogen compound
  • Amine
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Process

Naturally occurring process:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point168.64 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility22.3 g/LNot Available
LogP-1.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility22.3 g/LALOGPS
logP0.14ALOGPS
logP-1.5ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)11.52ChemAxon
pKa (Strongest Basic)-1.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area108.38 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity53.25 m³·mol⁻¹ChemAxon
Polarizability21.45 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00c3-9210000000-49e8caef8629bb5b3f0bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00or-7902000000-4e3542be1d6d35b1b0c4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0930000000-e2122f1423d3060097b9Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0790000000-e66897c78fa010a45ab8Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0cfs-0910000000-e4e73c07b687772a1108Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0900000000-99f619802e3ba7bd8b2eSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0900000000-18dd55d7372a11b9dfb7Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-1900000000-fdc016f6d17808e4cf1bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-5900000000-ec478d4dfe03f80b91adSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0790000000-0d953fc9632751f00f72Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-07xs-0920000000-0e8154089a57b6bef7c4Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0900000000-c54a530153a028d6ffccSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0900000000-1f4cd6bc7d377fe7731eSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0a4i-0900000000-c3cdcfa5d386ac7222faSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0aor-4900000000-337f45a27b7b12b1b2f0Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-03di-0920000000-52d24e07b71b7d08dcdbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0190000000-6d052797bc5b8b31bf7bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03dl-0900000000-01d92fca070f980c2668Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-0900000000-95712722811cd50ab160Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-0190000000-b97d64dba479bbac0253Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-03di-0930000000-fce77aa139fbedd4910bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0900000000-83efc18ba2f8876de391Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-6900000000-10cb8c7171afb23abcc4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0292-9200000000-6bc1af7531a9c978723cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-2970000000-6f2d6b7661e187a5d944Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02vi-7950000000-cec9468697b640599e3fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-91bfffe7dcfe08cb1abaSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00441 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00441 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00441
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID54753
KEGG Compound IDC07650
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkGemcitabine
METLIN IDNot Available
PubChem Compound60750
PDB IDNot Available
ChEBI ID175901
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB ID
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. (). FDA label . .
  2. BC Cancer Agency [Link]

Enzymes

General function:
Involved in ATP binding
Specific function:
Catalyzes specific phosphoryl transfer from ATP to UMP and CMP.
Gene Name:
CMPK1
Uniprot ID:
P30085
Molecular weight:
20180.12
References
  1. Vernejoul F, Ghenassia L, Souque A, Lulka H, Drocourt D, Cordelier P, Pradayrol L, Pyronnet S, Buscail L, Tiraby G: Gene therapy based on gemcitabine chemosensitization suppresses pancreatic tumor growth. Mol Ther. 2006 Dec;14(6):758-67. Epub 2006 Sep 25. [PubMed:17000136 ]
  2. Hsu CH, Liou JY, Dutschman GE, Cheng YC: Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium. Mol Pharmacol. 2005 Mar;67(3):806-14. Epub 2004 Nov 18. [PubMed:15550676 ]
  3. Maring JG, Groen HJ, Wachters FM, Uges DR, de Vries EG: Genetic factors influencing pyrimidine-antagonist chemotherapy. Pharmacogenomics J. 2005;5(4):226-43. [PubMed:16041392 ]
  4. Lam W, Leung CH, Bussom S, Cheng YC: The impact of hypoxic treatment on the expression of phosphoglycerate kinase and the cytotoxicity of troxacitabine and gemcitabine. Mol Pharmacol. 2007 Sep;72(3):536-44. Epub 2007 Jun 12. [PubMed:17565005 ]
General function:
Involved in ATP binding
Specific function:
Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents.
Gene Name:
DCK
Uniprot ID:
P27707
Molecular weight:
30518.315
References
  1. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966 ]
  2. Marechal R, Mackey JR, Lai R, Demetter P, Peeters M, Polus M, Cass CE, Salmon I, Deviere J, Van Laethem JL: Deoxycitidine kinase is associated with prolonged survival after adjuvant gemcitabine for resected pancreatic adenocarcinoma. Cancer. 2010 Nov 15;116(22):5200-6. doi: 10.1002/cncr.25303. [PubMed:20669326 ]
General function:
Involved in oxidation reduction
Specific function:
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Gene Name:
RRM1
Uniprot ID:
P23921
Molecular weight:
90069.375
References
  1. Kwon WS, Rha SY, Choi YH, Lee JO, Park KH, Jung JJ, Kim TS, Jeung HC, Chung HC: Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenet Genomics. 2006 Jun;16(6):429-38. [PubMed:16708051 ]
  2. Rosell R, Cobo M, Isla D, Camps C, Massuti B: Pharmacogenomics and gemcitabine. Ann Oncol. 2006 May;17 Suppl 5:v13-16. [PubMed:16807441 ]
  3. Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G: RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006 Oct 10;24(29):4731-7. Epub 2006 Sep 11. [PubMed:16966686 ]
  4. Smid K, Bergman AM, Eijk PP, Veerman G, van Haperen VW, van den Ijssel P, Ylstra B, Peters GJ: Micro-array analysis of resistance for gemcitabine results in increased expression of ribonucleotide reductase subunits. Nucleosides Nucleotides Nucleic Acids. 2006;25(9-11):1001-7. [PubMed:17065054 ]
  5. Nakahira S, Nakamori S, Tsujie M, Takahashi Y, Okami J, Yoshioka S, Yamasaki M, Marubashi S, Takemasa I, Miyamoto A, Takeda Y, Nagano H, Dono K, Umeshita K, Sakon M, Monden M: Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int J Cancer. 2007 Mar 15;120(6):1355-63. [PubMed:17131328 ]
  6. Cerqueira NM, Fernandes PA, Ramos MJ: Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry. 2007;13(30):8507-15. [PubMed:17636467 ]
General function:
Involved in thymidylate synthase activity
Specific function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular weight:
35715.65
References
  1. Rosell R, Taron M, Sanchez JM, Moran T, Reguart N, Besse B, Isla D, Massuti B, Alberola V, Sanchez JJ: The promise of pharmacogenomics: gemcitabine and pemetrexed. Oncology (Williston Park). 2004 Nov;18(13 Suppl 8):70-6. [PubMed:15655942 ]
  2. Huang CL, Yokomise H, Fukushima M, Kinoshita M: Tailor-made chemotherapy for non-small cell lung cancer patients. Future Oncol. 2006 Apr;2(2):289-99. [PubMed:16563096 ]
  3. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320 ]
  4. Zhao XD, Zhang Y: [Routine chemotherapeutic drug treatment effectiveness predictive molecules and chemotherapeutic drug selection]. Ai Zheng. 2006 Dec;25(12):1577-80. [PubMed:17166391 ]
  5. Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Del Tacca M, Danesi R: Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther. 2006 Jun;5(6):1387-95. [PubMed:16818496 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in zinc ion binding
Specific function:
This enzyme scavenge exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name:
CDA
Uniprot ID:
P32320
Molecular weight:
16184.545
References
  1. Giovannetti E, Laan AC, Vasile E, Tibaldi C, Nannizzi S, Ricciardi S, Falcone A, Danesi R, Peters GJ: Correlation between cytidine deaminase genotype and gemcitabine deamination in blood samples. Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):720-5. doi: 10.1080/15257770802145447. [PubMed:18600531 ]
  2. Gusella M, Pasini F, Bolzonella C, Meneghetti S, Barile C, Bononi A, Toso S, Menon D, Crepaldi G, Modena Y, Stievano L, Padrini R: Equilibrative nucleoside transporter 1 genotype, cytidine deaminase activity and age predict gemcitabine plasma clearance in patients with solid tumours. Br J Clin Pharmacol. 2011 Mar;71(3):437-44. doi: 10.1111/j.1365-2125.2010.03838.x. [PubMed:21284703 ]
  3. Wong A, Soo RA, Yong WP, Innocenti F: Clinical pharmacology and pharmacogenetics of gemcitabine. Drug Metab Rev. 2009;41(2):77-88. doi: 10.1080/03602530902741828. [PubMed:19514966 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Bergman AM, Pinedo HM, Talianidis I, Veerman G, Loves WJ, van der Wilt CL, Peters GJ: Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer. 2003 Jun 16;88(12):1963-70. [PubMed:12799644 ]
General function:
Involved in nucleoside transmembrane transporter activity
Specific function:
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs)
Gene Name:
SLC29A1
Uniprot ID:
Q99808
Molecular weight:
50218.8
References
  1. Santini D, Vincenzi B, Fratto ME, Perrone G, Lai R, Catalano V, Cass C, Ruffini PA, Spoto C, Muretto P, Rizzo S, Muda AO, Mackey JR, Russo A, Tonini G, Graziano F: Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer. J Cell Physiol. 2010 May;223(2):384-8. doi: 10.1002/jcp.22045. [PubMed:20082300 ]