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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2021-09-14 15:48:12 UTC
HMDB IDHMDB0014584
Secondary Accession Numbers
  • HMDB14584
Metabolite Identification
Common NameGemcitabine
DescriptionGemcitabine is a nucleoside analog used as chemotherapy. It is marketed as Gemzar by Eli Lilly and Company. As with fluorouracil and other analogues of pyrimidines, the drug replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as new nucleosides cannot be attached to the 'faulty' nucleoside, resulting in apoptosis (cellular 'suicide').
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

Source

Route of exposure

Process

Naturally occurring process

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point168.64 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility22.3 g/LNot Available
LogP-1.4Not Available
Experimental Spectral PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility22.3 g/LALOGPS
logP10(0.14) g/LALOGPS
logP10(-1.5) g/LChemAxon
logS10(-1.1) g/LALOGPS
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
Predicted Spectral Properties

Predicted Kovats Retention Indices

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Gemcitabine,1TMS,#1C[Si](C)(C)OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C(F)(F)[C@@H]1O2133.3Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,1TMS,#2C[Si](C)(C)O[C@@H]1[C@@H](CO)O[C@@H](N2C=CC(N)=NC2=O)C1(F)F2157.9Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,1TMS,#3C[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)C=C12231.3Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TMS,#1C[Si](C)(C)OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C(F)(F)[C@@H]1O[Si](C)(C)C2132.7Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TMS,#2C[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO[Si](C)(C)C)[C@@H](O)C2(F)F)C=C12200.7Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TMS,#3C[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O[Si](C)(C)C)C2(F)F)C=C12211.2Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TMS,#4C[Si](C)(C)N(C1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)C=C1)[Si](C)(C)C2178.7Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,1TBDMS,#1CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C(F)(F)[C@@H]1O2349.0Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,1TBDMS,#2CC(C)(C)[Si](C)(C)O[C@@H]1[C@@H](CO)O[C@@H](N2C=CC(N)=NC2=O)C1(F)F2362.9Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,1TBDMS,#3CC(C)(C)[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)C=C12471.3Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TBDMS,#1CC(C)(C)[Si](C)(C)OC[C@H]1O[C@@H](N2C=CC(N)=NC2=O)C(F)(F)[C@@H]1O[Si](C)(C)C(C)(C)C2577.4Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TBDMS,#2CC(C)(C)[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO[Si](C)(C)C(C)(C)C)[C@@H](O)C2(F)F)C=C12650.7Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TBDMS,#3CC(C)(C)[Si](C)(C)NC1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)C2(F)F)C=C12635.5Semi standard non polarhttps://arxiv.org/abs/1905.12712
Gemcitabine,2TBDMS,#4CC(C)(C)[Si](C)(C)N(C1=NC(=O)N([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)C=C1)[Si](C)(C)C(C)(C)C2620.5Semi standard non polarhttps://arxiv.org/abs/1905.12712
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Gemcitabine GC-MS (Non-derivatized) - 70eV, Positivesplash10-00c3-9210000000-49e8caef8629bb5b3f0b2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Gemcitabine GC-MS (2 TMS) - 70eV, Positivesplash10-00or-7902000000-4e3542be1d6d35b1b0c42017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Gemcitabine GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-03di-0930000000-e2122f1423d3060097b92017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-03di-0790000000-e66897c78fa010a45ab82017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0cfs-0910000000-e4e73c07b687772a11082017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-0900000000-99f619802e3ba7bd8b2e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-0900000000-18dd55d7372a11b9dfb72017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-1900000000-fdc016f6d17808e4cf1b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-5900000000-ec478d4dfe03f80b91ad2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-03di-0790000000-0d953fc9632751f00f722017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-07xs-0920000000-0e8154089a57b6bef7c42017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-0900000000-c54a530153a028d6ffcc2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-0900000000-1f4cd6bc7d377fe7731e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0a4i-0900000000-c3cdcfa5d386ac7222fa2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-0aor-4900000000-337f45a27b7b12b1b2f02017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine LC-ESI-ITFT , negative-QTOFsplash10-03di-0920000000-52d24e07b71b7d08dcdb2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 90V, Negative-QTOFsplash10-0a4i-5900000000-ec478d4dfe03f80b91ad2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 75V, Negative-QTOFsplash10-0a4i-1900000000-fdc016f6d17808e4cf1b2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 30V, Negative-QTOFsplash10-0cfs-0910000000-e4e73c07b687772a11082021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 15V, Negative-QTOFsplash10-03di-0790000000-e66897c78fa010a45ab82021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 45V, Negative-QTOFsplash10-0a4i-0900000000-99f619802e3ba7bd8b2e2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 60V, Negative-QTOFsplash10-0a4i-0900000000-18dd55d7372a11b9dfb72021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 35V, Negative-QTOFsplash10-03di-0930000000-23c49f9312028218d2e12021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 30V, Negative-QTOFsplash10-07xs-0920000000-0e8154089a57b6bef7c42021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 60V, Negative-QTOFsplash10-0a4i-0900000000-1f4cd6bc7d377fe7731e2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 75V, Negative-QTOFsplash10-0a4i-0900000000-c3cdcfa5d386ac7222fa2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Gemcitabine 45V, Negative-QTOFsplash10-0a4i-0900000000-c54a530153a028d6ffcc2021-09-20HMDB team, MONAView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
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 IDNot Available
Good Scents IDNot Available
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 ]