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Identification
NamePemetrexed
Accession NumberDB00642  (APRD00573, EXPT02075)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.

Structure
Thumb
SynonymsNot Available
External Identifiers
  • LY-231514
  • LY231514
  • NSC-698037
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Alimtainjection, powder, lyophilized, for solution100 mg/4mLintravenousEli Lilly and Company2008-01-15Not applicableUs
Alimtapowder for solution500 mgintravenousEli Lilly Canada Inc2004-08-03Not applicableCanada
Alimtainjection, powder, lyophilized, for solution500 mg/20mLintravenousEli Lilly and Company2004-02-13Not applicableUs
Alimtapowder for solution100 mgintravenousEli Lilly Canada Inc2009-01-09Not applicableCanada
Pemetrexed Disodium for Injectionpowder for solution1000 mgintravenousHospira Healthcare CorporationNot applicableNot applicableCanada
Pemetrexed Disodium for Injectionpowder for solution500 mgintravenousHospira Healthcare CorporationNot applicableNot applicableCanada
Pemetrexed Disodium for Injectionpowder for solution100 mgintravenousHospira Healthcare CorporationNot applicableNot applicableCanada
Pemetrexed Disodium for Injectionpowder for solution500 mgintravenousTeva Canada LimitedNot applicableNot applicableCanada
Taro-pemetrexedpowder for solution500 mgintravenousTaro Pharmaceuticals IncNot applicableNot applicableCanada
Taro-pemetrexedpowder for solution100 mgintravenousTaro Pharmaceuticals IncNot applicableNot applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Pemetrexed disodium
150399-23-8
Thumb
  • InChI Key: NYDXNILOWQXUOF-GXKRWWSZSA-L
  • Monoisotopic Mass: 471.11307191
  • Average Mass: 471.381
DBSALT000846
Pemetrexed disodium hemipentahydrate
357166-30-4
Thumb
  • InChI Key: ZCTCZKWJFTYNMZ-WKUCUCPSSA-J
  • Monoisotopic Mass: 1032.27896725
  • Average Mass: 1032.836
DBSALT001782
Pemetrexed disodium heptahydrate
357166-29-1
Thumb
  • InChI Key: QJVSMHJWAOSBMD-MYXYZBIASA-L
  • Monoisotopic Mass: 597.1870247
  • Average Mass: 597.486
DBSALT001641
Categories
UNII04Q9AIZ7NO
CAS number137281-23-3
WeightAverage: 427.4106
Monoisotopic: 427.149183429
Chemical FormulaC20H21N5O6
InChI KeyWBXPDJSOTKVWSJ-ZDUSSCGKSA-N
InChI
InChI=1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m0/s1
IUPAC Name
(2S)-2-{[4-(2-{4-hydroxy-2-imino-1H,2H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)phenyl]formamido}pentanedioic acid
SMILES
[H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(CCC2=CNC3=C2C(O)=NC(=N)N3)C=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hippuric acids. These are compounds containing hippuric acid, which consists of a of a benzoyl group linked to the N-terminal of a glycine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentHippuric acids
Alternative Parents
Substituents
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Hippuric acid
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Pyrrolopyrimidine
  • Benzoic acid or derivatives
  • Benzoyl
  • Pyrimidone
  • Amino fatty acid
  • Fatty acyl
  • Substituted pyrrole
  • Pyrimidine
  • Primary aromatic amine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Vinylogous amide
  • Pyrrole
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
PharmacodynamicsPreclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.
Mechanism of actionPemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Related Articles
AbsorptionNot Available
Volume of distribution
  • 16.1 L
Protein binding81%
Metabolism

Metabolized by Cytochrome P450 Enzymes

Route of eliminationPemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration.
Half life3.5 hours
Clearance
  • 91.8 mL/min [Cancer patients with normal renal function receiving 0.2 to 838 mg/m2 infusion over a 10-minute period]
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6997
Blood Brain Barrier+0.7542
Caco-2 permeable-0.819
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.9729
P-glycoprotein inhibitor IINon-inhibitor0.9825
Renal organic cation transporterNon-inhibitor0.8923
CYP450 2C9 substrateNon-substrate0.7547
CYP450 2D6 substrateNon-substrate0.8204
CYP450 3A4 substrateNon-substrate0.6051
CYP450 1A2 substrateNon-inhibitor0.912
CYP450 2C9 inhibitorNon-inhibitor0.8938
CYP450 2D6 inhibitorNon-inhibitor0.9117
CYP450 2C19 inhibitorNon-inhibitor0.8844
CYP450 3A4 inhibitorNon-inhibitor0.8253
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9508
Ames testNon AMES toxic0.8528
CarcinogenicityNon-carcinogens0.964
BiodegradationNot ready biodegradable0.8296
Rat acute toxicity2.5023 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9624
hERG inhibition (predictor II)Non-inhibitor0.8718
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
Packagers
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionintravenous100 mg/4mL
Injection, powder, lyophilized, for solutionintravenous500 mg/20mL
Powder for solutionintravenous100 mg
Powder for solutionintravenous500 mg
Powder for solutionintravenous1000 mg
Prices
Unit descriptionCostUnit
Alimta 500 mg Solution Vial3154.94USD vial
Alimta 500 mg vial3033.6USD vial
Alimta 100 mg vial606.72USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA1340794 No1999-10-192016-10-19Canada
CA2400155 No2009-09-152021-02-12Canada
US5217974 No1994-03-292011-03-29Us
US5344932 Yes1997-01-242017-01-24Us
US7772209 Yes2002-05-242022-05-24Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0905 mg/mLALOGPS
logP-0.19ALOGPS
logP-0.25ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)3.34ChemAxon
pKa (Strongest Basic)7.13ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area187.96 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity120.46 m3·mol-1ChemAxon
Polarizability43.06 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5344932
General References
  1. Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. [PubMed:16291410 ]
  2. Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic]. Bull Cancer. 2007;94 Spec No Actualites:S134-8. [PubMed:17845983 ]
  3. Fuld AD, Dragnev KH, Rigas JR: Pemetrexed in advanced non-small-cell lung cancer. Expert Opin Pharmacother. 2010 Jun;11(8):1387-402. doi: 10.1517/14656566.2010.482560. [PubMed:20446853 ]
  4. Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. [PubMed:12722874 ]
External Links
ATC CodesL01BA04
AHFS Codes
  • 10:00.00
PDB Entries
FDA labelDownload (233 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ClozapineThe risk or severity of adverse effects can be increased when Pemetrexed is combined with Clozapine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Pemetrexed.
DesmopressinThe serum concentration of Pemetrexed can be increased when it is combined with Desmopressin.
DiclofenacThe serum concentration of Pemetrexed can be increased when it is combined with Diclofenac.
DiflunisalThe serum concentration of Pemetrexed can be increased when it is combined with Diflunisal.
EtodolacThe serum concentration of Pemetrexed can be increased when it is combined with Etodolac.
FenoprofenThe serum concentration of Pemetrexed can be increased when it is combined with Fenoprofen.
FloctafenineThe serum concentration of Pemetrexed can be increased when it is combined with Floctafenine.
FlurbiprofenThe serum concentration of Pemetrexed can be increased when it is combined with Flurbiprofen.
IbuprofenThe serum concentration of Pemetrexed can be increased when it is combined with Ibuprofen.
IndomethacinThe serum concentration of Pemetrexed can be increased when it is combined with Indomethacin.
KetoprofenThe serum concentration of Pemetrexed can be increased when it is combined with Ketoprofen.
KetorolacThe serum concentration of Pemetrexed can be increased when it is combined with Ketorolac.
LeflunomideThe risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide.
Mefenamic acidThe serum concentration of Pemetrexed can be increased when it is combined with Mefenamic acid.
MeloxicamThe serum concentration of Pemetrexed can be increased when it is combined with Meloxicam.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Pemetrexed.
NabumetoneThe serum concentration of Pemetrexed can be increased when it is combined with Nabumetone.
NaproxenThe serum concentration of Pemetrexed can be increased when it is combined with Naproxen.
NatalizumabThe risk or severity of adverse effects can be increased when Pemetrexed is combined with Natalizumab.
OxaprozinThe serum concentration of Pemetrexed can be increased when it is combined with Oxaprozin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pemetrexed.
PiroxicamThe serum concentration of Pemetrexed can be increased when it is combined with Piroxicam.
RoflumilastRoflumilast may increase the immunosuppressive activities of Pemetrexed.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Pemetrexed.
SulindacThe serum concentration of Pemetrexed can be increased when it is combined with Sulindac.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Pemetrexed.
Tiaprofenic acidThe serum concentration of Pemetrexed can be increased when it is combined with Tiaprofenic acid.
TofacitinibPemetrexed may increase the immunosuppressive activities of Tofacitinib.
TolmetinThe serum concentration of Pemetrexed can be increased when it is combined with Tolmetin.
TrastuzumabTrastuzumab may increase the neutropenic activities of Pemetrexed.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
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. Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [PubMed:11252887 ]
  2. Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555 ]
  3. Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245 ]
  4. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712 ]
  5. Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [PubMed:11763166 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Schultz RM, Dempsey JA: Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Anticancer Res. 2001 Sep-Oct;21(5):3209-14. [PubMed:11848474 ]
  8. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793 ]
  9. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699 ]
  10. 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 ]
  11. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein homodimerization activity
Specific Function:
Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).
Gene Name:
ATIC
Uniprot ID:
P31939
Molecular Weight:
64615.255 Da
References
  1. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811 ]
  2. Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555 ]
  3. Racanelli AC, Rothbart SB, Heyer CL, Moran RG: Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res. 2009 Jul 1;69(13):5467-74. doi: 10.1158/0008-5472.CAN-08-4979. Epub 2009 Jun 23. [PubMed:19549896 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555 ]
  2. Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [PubMed:11763166 ]
  3. Mauritz R, Peters GJ, Priest DG, Assaraf YG, Drori S, Kathmann I, Noordhuis P, Bunni MA, Rosowsky A, Schornagel JH, Pinedo HM, Jansen G: Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol. 2002 Jan 15;63(2):105-15. [PubMed:11841783 ]
  4. Schultz RM, Dempsey JA: Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Anticancer Res. 2001 Sep-Oct;21(5):3209-14. [PubMed:11848474 ]
  5. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  7. Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [PubMed:11252887 ]
  8. Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245 ]
  9. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712 ]
  10. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699 ]
  11. 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 ]
  12. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Phosphoribosylglycinamide formyltransferase activity
Specific Function:
Not Available
Gene Name:
GART
Uniprot ID:
P22102
Molecular Weight:
107766.295 Da
References
  1. Schultz RM, Dempsey JA: Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Anticancer Res. 2001 Sep-Oct;21(5):3209-14. [PubMed:11848474 ]
  2. Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555 ]
  3. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699 ]
  4. 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 ]
  5. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811 ]
  6. Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [PubMed:11252887 ]
  7. Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245 ]
  8. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712 ]
  9. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793 ]
  10. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
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. De Pas TM, Toffalorio F, Giovannetti E, Radice D, Russo F, Angeli I, Calamai G, Spitaleri G, Catania C, Noberasco C, Milani A, Pelosi G, Danesi R, De Braud F: Optimizing pemetrexed-gemcitabine combination in patients with advanced non-small cell lung cancer: a pharmacogenetic approach. J Thorac Oncol. 2011 Apr;6(4):768-73. doi: 10.1097/JTO.0b013e31820d7818. [PubMed:21336182 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
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. De Pas TM, Toffalorio F, Giovannetti E, Radice D, Russo F, Angeli I, Calamai G, Spitaleri G, Catania C, Noberasco C, Milani A, Pelosi G, Danesi R, De Braud F: Optimizing pemetrexed-gemcitabine combination in patients with advanced non-small cell lung cancer: a pharmacogenetic approach. J Thorac Oncol. 2011 Apr;6(4):768-73. doi: 10.1097/JTO.0b013e31820d7818. [PubMed:21336182 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 29, 2016 03:21