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Identification
NameGemcitabine
Accession NumberDB00441  (APRD00201)
TypeSmall Molecule
GroupsApproved
Description

Gemcitabine 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”).
Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in oesophageal cancer, and is used experimentally in lymphomas and various other tumor types.

Structure
Thumb
Synonyms
2'-Deoxy-2',2'-difluorocytidine
2',2'-Difluorodeoxycytidine
4-amino-1-((2R,4R,5R)-3,3-Difluoro-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-one
Gemcitabin
Gemcitabina
Gemcitabine
Gemcitabinum
External Identifiers
  • LY-188011
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Gemcitabinesolution38 mgintravenousActavis Pharma CompanyNot applicableNot applicableCanada
Act Gemcitabinepowder for solution1 gintravenousActavis Pharma CompanyNot applicableNot applicableCanada
Act Gemcitabinepowder for solution200 mgintravenousActavis Pharma CompanyNot applicableNot applicableCanada
Aj-gemcitabinepowder for solution1 gintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Aj-gemcitabinepowder for solution2 gintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Aj-gemcitabinepowder for solution200 mgintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Gemcitabineinjection, solution38 mg/mLintravenousHospira, Inc.2011-08-04Not applicableUs
Gemcitabineinjection, solution38 mg/mLintravenousHospira, Inc.2011-08-04Not applicableUs
Gemcitabineinjection, solution38 mg/mLintravenousHospira, Inc.2011-08-04Not applicableUs
Gemcitabine for Injectionpowder for solution200 mgintravenousAlveda Pharmaceuticals IncNot applicableNot applicableCanada
Gemcitabine for Injectionpowder for solution2 gintravenousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Gemcitabine for Injectionpowder for solution1 gintravenousTeva Canada Limited2008-06-27Not applicableCanada
Gemcitabine for Injectionpowder for solution1 gintravenousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Gemcitabine for Injectionpowder for solution200 mgintravenousTeva Canada Limited2008-09-10Not applicableCanada
Gemcitabine for Injectionpowder for solution200 mgintravenousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Gemcitabine for Injectionpowder for solution2 gintravenousAccord Healthcare Inc2011-08-31Not applicableCanada
Gemcitabine for Injectionpowder for solution1 gintravenousAccord Healthcare Inc2009-07-16Not applicableCanada
Gemcitabine for Injectionpowder for solution200 mgintravenousAccord Healthcare Inc2011-08-31Not applicableCanada
Gemcitabine for Injectionpowder for solution1 gintravenousAlveda Pharmaceuticals IncNot applicableNot applicableCanada
Gemcitabine for Injection Concentratesolution100 mgintravenousAccord Healthcare Inc2014-04-17Not applicableCanada
Gemcitabine for Injection USPpowder for solution1 gintravenousGeneric Medical Partners IncNot applicableNot applicableCanada
Gemcitabine for Injection USPpowder for solution200 mgintravenousGeneric Medical Partners IncNot applicableNot applicableCanada
Gemcitabine for Injection, USPpowder for solution2 gintravenousHospira Healthcare Corporation2009-10-01Not applicableCanada
Gemcitabine for Injection, USPpowder for solution1 gintravenousHospira Healthcare Corporation2007-12-272014-08-01Canada
Gemcitabine for Injection, USPpowder2 gintravenousDr Reddys Laboratories LtdNot applicableNot applicableCanada
Gemcitabine for Injection, USPpowder for solution2 gintravenousMylan Pharmaceuticals Ulc2014-06-26Not applicableCanada
Gemcitabine for Injection, USPpowder1 gintravenousDr Reddys Laboratories LtdNot applicableNot applicableCanada
Gemcitabine for Injection, USPpowder for solution1 gintravenousMylan Pharmaceuticals Ulc2014-06-26Not applicableCanada
Gemcitabine for Injection, USPpowder200 mgintravenousDr Reddys Laboratories LtdNot applicableNot applicableCanada
Gemcitabine for Injection, USPpowder for solution200 mgintravenousHospira Healthcare Corporation2008-01-25Not applicableCanada
Gemcitabine for Injection, USPpowder for solution200 mgintravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Gemcitabine Hydrochloride for Injectionpowder for solution1 gintravenousSandoz Canada Incorporated2007-11-20Not applicableCanada
Gemcitabine Hydrochloride for Injectionpowder for solution200 mgintravenousSandoz Canada Incorporated2007-11-20Not applicableCanada
Gemcitabine Injectionsolution40 mgintravenousSandoz Canada Incorporated2013-09-24Not applicableCanada
Gemcitabine Injectionsolution38 mgintravenousHospira Healthcare Corporation2013-03-20Not applicableCanada
Gemcitabine Sun for Injectionpowder for solution1 gintravenousTaro Pharmaceuticals Inc2013-03-21Not applicableCanada
Gemcitabine Sun for Injectionpowder for solution200 mgintravenousTaro Pharmaceuticals Inc2013-03-21Not applicableCanada
Gemzarinjection, powder, lyophilized, for solution200 mg/5mLintravenousEli Lilly and Company1996-05-22Not applicableUs
Gemzarinjection, powder, lyophilized, for solution1 g/25mLintravenousEli Lilly and Company1996-05-22Not applicableUs
Gemzar (1gm/vial)powder for solution1 gintravenousEli Lilly Canada Inc1997-04-172015-11-01Canada
Gemzar (200mg/vial)powder for solution200 mgintravenousEli Lilly Canada Inc1997-04-17Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Gemcitabineinjection, powder, lyophilized, for solution200 mg/5mLintravenousSun Pharma Global FZE2011-07-25Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution200 mg/5mLintravenousSagent Pharmaceuticals2011-07-25Not applicableUs
Gemcitabineinjection38 mg/mLintravenousActavis Pharma, Inc.2016-04-12Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution1 g/26.3mLintravenousFresenius Kabi USA, LLC2011-07-26Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution38 mg/mLintravenousHospira, Inc.2010-11-15Not applicableUs
Gemcitabineinjection38 mg/mLintravenousActavis Pharma, Inc.2016-04-12Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution200 mg/5.26mLintravenousFresenius Kabi USA, LLC2011-07-26Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution38 mg/mLintravenousHospira, Inc.2011-07-25Not applicableUs
Gemcitabineinjection38 mg/mLintravenousActavis Pharma, Inc.2016-04-12Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution40 mg/mLintravenousBedford Laboratories2012-03-19Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution38 mg/mLintravenousHospira, Inc.2011-07-25Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution1 g/25mLintravenousDr. Reddy's Laboratories Limited2011-07-25Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution1 g/25mLintravenousSagent Pharmaceuticals2014-12-29Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution200 mg/5mLintravenousDr. Reddy's Laboratories Limited2011-07-25Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution200 mg/5mLintravenousSagent Pharmaceuticals2014-12-29Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution1 g/25mLintravenousSun Pharma Global FZE2011-07-25Not applicableUs
Gemcitabineinjection, powder, lyophilized, for solution1 g/25mLintravenousSagent Pharmaceuticals2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousMylan Institutional LLC2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousAccord Healthcare Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousPfizer Laboratories Div Pfizer Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution2 g/50mLintravenousMylan Institutional LLC2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousWatson Laboratories, Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution2 g/50mLintravenousAPP Pharmaceuticals, LLC2011-05-162016-01-09Us
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousActavis Pharma, Inc.2015-01-05Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousWatson Laboratories, Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousActavis Pharma, Inc.2015-01-05Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenoushameln rds gmbh2012-09-20Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenoushameln rds gmbh2012-09-20Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousHeritage Pharmaceuticals Inc.2012-10-22Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousGland Pharma Limited2016-02-01Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousGland Pharma Limited2016-02-01Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution2 g/50mLintravenousAccord Healthcare Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution2 g/50mLintravenousPfizer Laboratories Div Pfizer Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousAccord Healthcare Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution1 g/25mLintravenousPfizer Laboratories Div Pfizer Inc.2011-07-25Not applicableUs
Gemcitabine Hydrochlorideinjection, powder, lyophilized, for solution200 mg/5mLintravenousMylan Institutional LLC2011-07-25Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AbineDosa
AbingemMiracalus
AcytabinIntas
CelgemAlkem
CelzarCelon
CytogemDr Reddys
DaplaxDr Reddys
DercinEgis
EriogemEriochem
FotinexFada
GebinaAspen
GembioBioprofarma
GemciredDr Reddys
GemitaFresenius
GeztRichmond
GitrabinActavis
GramagenLilly
JemtaSandoz
NallianGedeon Richter
OncogemGrey Inversiones
RibozarRibosepharm
TabinCrinos
XtrozRanbaxy
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Gemcitabine Hydrochloride
122111-03-9
Thumb
  • InChI Key: OKKDEIYWILRZIA-OSZBKLCCSA-N
  • Monoisotopic Mass: 299.048440004
  • Average Mass: 299.659
DBSALT000092
Categories
UNIIB76N6SBZ8R
CAS number95058-81-4
WeightAverage: 263.1981
Monoisotopic: 263.071762265
Chemical FormulaC9H11F2N3O4
InChI KeyInChIKey=SDUQYLNIPVEERB-QPPQHZFASA-N
InChI
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
IUPAC Name
4-amino-1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidin-2-one
SMILES
NC1=NC(=O)N(C=C1)[C@@H]1O[[email protected]](CO)[C@@H](O)C1(F)F
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These 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
  • Pyrimidone
  • Aminopyrimidine
  • Imidolactam
  • Pyrimidine
  • Primary aromatic amine
  • Hydropyrimidine
  • Saccharide
  • Heteroaromatic compound
  • Oxolane
  • Secondary alcohol
  • Halohydrin
  • Fluorohydrin
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary amine
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Organofluoride
  • Organohalogen compound
  • Amine
  • Alkyl halide
  • Alkyl fluoride
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationGemcitabine is indicated for the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy; metastatic ovarian cancer; inoperable, locally advanced (Stage IIIA or IIIB), or metastatic (Stage IV) non-small cell lung cancer; and locally advanced (nonresectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas.
PharmacodynamicsGemcitabine is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (or DNA synthesis phase of the cell cycle), stopping normal development and division. Gemcitabine blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Gemcitabine blocks the incorporation of the thymidine nucleotide into the DNA strand. It demonstrates dose-dependent synergistic activity with cisplatin in vitro. In vivo, gemcitabine showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Gemcitabine was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to gemcitabine 4 hours before cisplatin produced the greatest interaction.
Mechanism of actionGemcitabine inhibits thymidylate synthetase, leading to inhibition of DNA synthesis and cell death. Gemcitabine is a prodrug so activity occurs as a result of intracellular conversion to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate by deoxycitidine kinase. Gemcitabine diphosphate also inhibits ribonucleotide reductase, the enzyme responsible for catalyzing synthesis of deoxynucleoside triphosphates required for DNA synthesis. Finally, Gemcitabine triphosphate (diflurorodeoxycytidine triphosphate) competes with endogenous deoxynucleoside triphosphates for incorporation into DNA.
Related Articles
AbsorptionThe pharmacokinetics of gemcitabine are described by a 2-compartment model.
Volume of distribution
  • 50 L/m^2 [infusions lasting <70 minutes]
  • 370 L/m^2 [long infusions]
Protein bindingPlasma protein binding is negligible (<10%)
Metabolism

Transformed via nucleoside kinases to two active metabolites, gemcitabine diphosphate and gemcitabine triphosphate. Can also undergo deamination via cytidine deaminase to an inactive uracil metabolite (dFdU).

SubstrateEnzymesProduct
Gemcitabine
Gemcitabine MonophosphateDetails
Gemcitabine Monophosphate
Difluorodeoxyuridine monophosphateDetails
Gemcitabine Monophosphate
Gemcitabine diphosphateDetails
Gemcitabine diphosphate
Gemcitabine triphosphateDetails
Route of eliminationWithin one (1) week, 92% to 98% of the dose was recovered, almost entirely in the urine. Gemcitabine (<10%) and the inactive uracil metabolite, 2´-deoxy-2´,2´-difluorouridine (dFdU), accounted for 99% of the excreted dose.
Half lifeGemcitabine half-life for short infusions ranged from 42 to 94 minutes, and the value for long infusions varied from 245 to 638 minutes, depending on age and gender, reflecting a greatly increased volume of distribution with longer infusions.
Clearance
  • 92.2 L/hr/m2 [Men 29 yrs]
  • 75.7 L/hr/m2 [Men 45 yrs]
  • 55.1 L/hr/m2 [Men 65 yrs]
  • 40.7 L/hr/m2 [Men 79 yrs]
  • 69.4 L/hr/m2 [Women 29 yrs]
  • 57 L/hr/m2 [Women 45 yrs]
  • 41.5 L/hr/m2 [Women 65 yrs]
  • 30.7 L/hr/m2 [Women 79 yrs]
ToxicityMyelosuppression, paresthesias, and severe rash were the principal toxicities, LD50=500 mg/kg (orally in mice and rats)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Gemcitabine Action PathwayDrug actionSMP00446
Gemcitabine Metabolism PathwayDrug metabolismSMP00603
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug Reactions
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
Ribonucleoside-diphosphate reductase large subunit
Gene symbol: RRM1
UniProt: P23921
rs3177016 Not AvailableA AlleleNeutropenia17602053
Ribonucleoside-diphosphate reductase large subunit
Gene symbol: RRM1
UniProt: P23921
rs1042858 Not AvailableG AlleleNeutropenia17602053
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9814
Blood Brain Barrier+0.9693
Caco-2 permeable-0.8957
P-glycoprotein substrateNon-substrate0.8317
P-glycoprotein inhibitor INon-inhibitor0.9557
P-glycoprotein inhibitor IINon-inhibitor0.9106
Renal organic cation transporterNon-inhibitor0.939
CYP450 2C9 substrateNon-substrate0.8634
CYP450 2D6 substrateNon-substrate0.8484
CYP450 3A4 substrateNon-substrate0.6016
CYP450 1A2 substrateNon-inhibitor0.8958
CYP450 2C9 inhibitorNon-inhibitor0.8633
CYP450 2D6 inhibitorNon-inhibitor0.8787
CYP450 2C19 inhibitorNon-inhibitor0.8478
CYP450 3A4 inhibitorNon-inhibitor0.9032
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8862
Ames testNon AMES toxic0.6793
CarcinogenicityNon-carcinogens0.8286
BiodegradationNot ready biodegradable0.9948
Rat acute toxicity2.1220 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9948
hERG inhibition (predictor II)Non-inhibitor0.8314
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Teva parenteral medicines inc
  • Eli lilly and co
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous38 mg/mL
Injection, powder, lyophilized, for solutionintravenous1 g/26.3mL
Injection, powder, lyophilized, for solutionintravenous200 mg/5.26mL
Injection, powder, lyophilized, for solutionintravenous38 mg/mL
Injection, powder, lyophilized, for solutionintravenous40 mg/mL
Injection, solutionintravenous38 mg/mL
Solutionintravenous100 mg
Powderintravenous1 g
Powderintravenous2 g
Powderintravenous200 mg
Powder for solutionintravenous2 g
Injection, powder, lyophilized, for solutionintravenous2 g/50mL
Powder for solutionintravenous1 g
Solutionintravenous38 mg
Solutionintravenous40 mg
Injection, powder, lyophilized, for solutionintravenous1 g/25mL
Injection, powder, lyophilized, for solutionintravenous200 mg/5mL
Powder for solutionintravenous200 mg
Prices
Unit descriptionCostUnit
Gemzar 1 gm Solution Vial903.93USD vial
Gemzar 1 gram vial869.16USD vial
Gemzar 200 mg Solution Vial180.78USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4808614 No1993-05-152010-05-15Us
US5464826 No1993-05-072013-05-07Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point168.64 °CNot Available
water solubilitySolubleNot Available
logP-1.4Not Available
pKa3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility22.3 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity53.25 m3·mol-1ChemAxon
Polarizability21.45 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

John A. Weigel, “Process for making gemcitabine hydrochloride.” U.S. Patent US6001994, issued May, 1995.

US6001994
General References
  1. Link [Link]
External Links
ATC CodesL01BC05
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelDownload (105 KB)
MSDSDownload (69.2 KB)
Interactions
Drug Interactions
Drug
BleomycinThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Bleomycin.
ClozapineThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Gemcitabine.
FluorouracilThe serum concentration of Fluorouracil can be increased when it is combined with Gemcitabine.
LeflunomideThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Leflunomide.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Gemcitabine.
NatalizumabThe risk or severity of adverse effects can be increased when Gemcitabine is combined with Natalizumab.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Gemcitabine.
RoflumilastRoflumilast may increase the immunosuppressive activities of Gemcitabine.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Gemcitabine.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Gemcitabine.
TofacitinibGemcitabine may increase the immunosuppressive activities of Tofacitinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Gemcitabine.
WarfarinGemcitabine may increase the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Hastak K, Alli E, Ford JM: Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-Ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010 Oct 15;70(20):7970-80. doi: 10.1158/0008-5472.CAN-09-4521. Epub 2010 Aug 26. [PubMed:20798217 ]
  2. Ledermann JA, Gabra H, Jayson GC, Spanswick VJ, Rustin GJ, Jitlal M, James LE, Hartley JA: Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin Cancer Res. 2010 Oct 1;16(19):4899-905. doi: 10.1158/1078-0432.CCR-10-0832. Epub 2010 Aug 18. [PubMed:20719935 ]
  3. Garcia-Diaz M, Murray MS, Kunkel TA, Chou KM: Interaction between DNA Polymerase lambda and anticancer nucleoside analogs. J Biol Chem. 2010 May 28;285(22):16874-9. doi: 10.1074/jbc.M109.094391. Epub 2010 Mar 26. [PubMed:20348107 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Ribonucleoside-diphosphate reductase activity, thioredoxin disulfide as acceptor
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 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Thymidylate synthase activity
Specific Function:
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name:
TYMS
Uniprot ID:
P04818
Molecular Weight:
35715.65 Da
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 ]
  7. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Uridylate kinase activity
Specific Function:
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.
Gene Name:
CMPK1
Uniprot ID:
P30085
Molecular Weight:
22222.175 Da
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 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Zinc ion binding
Specific Function:
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
Gene Name:
CDA
Uniprot ID:
P32320
Molecular Weight:
16184.545 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Protein homodimerization activity
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 Da
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Atpase activity, coupled to transmembrane movement of substances
Specific Function:
ATP-dependent transporter probably involved in cellular detoxification through lipophilic anion extrusion.
Gene Name:
ABCC10
Uniprot ID:
Q5T3U5
Molecular Weight:
161627.375 Da
References
  1. Hopper-Borge E, Xu X, Shen T, Shi Z, Chen ZS, Kruh GD: Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 2009 Jan 1;69(1):178-84. doi: 10.1158/0008-5472.CAN-08-1420. [PubMed:19118001 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
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:
50218.805 Da
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 ]
  2. Marce S, Molina-Arcas M, Villamor N, Casado FJ, Campo E, Pastor-Anglada M, Colomer D: Expression of human equilibrative nucleoside transporter 1 (hENT1) and its correlation with gemcitabine uptake and cytotoxicity in mantle cell lymphoma. Haematologica. 2006 Jul;91(7):895-902. [PubMed:16818276 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function:
Sodium-dependent and pyrimidine-selective. Exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit) (selective for pyrimidine nucleosides and adenosine). It also transports the antiviral pyrimidine nucleoside analogs 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). It may be involved in the intestinal absorption and renal handling of ...
Gene Name:
SLC28A1
Uniprot ID:
O00337
Molecular Weight:
71583.18 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Nucleoside transmembrane transporter activity
Specific Function:
Mediates equilibrative transport of purine, pyrimidine nucleosides and the purine base hypoxanthine. Very less sensitive than SLC29A1 to inhibition by nitrobenzylthioinosine (NBMPR), dipyridamole, dilazep and draflazine.
Gene Name:
SLC29A2
Uniprot ID:
Q14542
Molecular Weight:
50112.335 Da
References
  1. Mackey JR, Yao SY, Smith KM, Karpinski E, Baldwin SA, Cass CE, Young JD: Gemcitabine transport in xenopus oocytes expressing recombinant plasma membrane mammalian nucleoside transporters. J Natl Cancer Inst. 1999 Nov 3;91(21):1876-81. [PubMed:10547395 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Pyrimidine- and adenine-specific:sodium symporter activity
Specific Function:
Sodium-dependent, pyrimidine- and purine-selective. Involved in the homeostasis of endogenous nucleosides. Exhibits the transport characteristics of the nucleoside transport system cib or N3 subtype (N3/cib) (with marked transport of both thymidine and inosine). Employs a 2:1 sodium/nucleoside ratio. Also able to transport gemcitabine, 3'-azido-3'-deoxythymidine (AZT), ribavirin and 3-deazaurid...
Gene Name:
SLC28A3
Uniprot ID:
Q9HAS3
Molecular Weight:
76929.61 Da
References
  1. Govindarajan R, Leung GP, Zhou M, Tse CM, Wang J, Unadkat JD: Facilitated mitochondrial import of antiviral and anticancer nucleoside drugs by human equilibrative nucleoside transporter-3. Am J Physiol Gastrointest Liver Physiol. 2009 Apr;296(4):G910-22. doi: 10.1152/ajpgi.90672.2008. Epub 2009 Jan 22. [PubMed:19164483 ]
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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10