Identification

Name
Pemetrexed
Accession Number
DB00642
Description

Pemetrexed is a chemotherapy drug that is manufactured and marketed by Eli Lilly and Company under the brand name Alimta. It is indicated for use in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are otherwise not candidates for curative surgery. Its use in non-small cell lung cancer has also been investigated.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 427.4106
Monoisotopic: 427.149183429
Chemical Formula
C20H21N5O6
Synonyms
  • Pemetrexed
External IDs
  • LY-231514
  • LY231514
  • NSC-698037

Pharmacology

Pharmacology
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Indication

Used 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

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Preclinical 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 action

Pemetrexed 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.

TargetActionsOrganism
AThymidylate synthase
inhibitor
Humans
ABifunctional purine biosynthesis protein PURH
inhibitor
Humans
ADihydrofolate reductase
inhibitor
Humans
ATrifunctional purine biosynthetic protein adenosine-3
inhibitor
Humans
Absorption
Not Available
Volume of distribution
  • 16.1 L
Protein binding

81%

Metabolism

Metabolized by Cytochrome P450 Enzymes

Route of elimination

Pemetrexed 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-life

3.5 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]
Adverse Effects
Medicalerrors
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Pemetrexed which could result in a higher serum level.
AbametapirThe serum concentration of Pemetrexed can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pemetrexed can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Pemetrexed.
AbirateroneThe serum concentration of Pemetrexed can be increased when it is combined with Abiraterone.
AceclofenacAceclofenac may decrease the excretion rate of Pemetrexed which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pemetrexed which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Pemetrexed.
AcetaminophenAcetaminophen may decrease the excretion rate of Pemetrexed which could result in a higher serum level.
AcetazolamideThe therapeutic efficacy of Pemetrexed can be increased when used in combination with Acetazolamide.
Interactions
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Food Interactions
  • Administer folic acid supplement. Folic acid supplement of 400 to 1000 mcg daily should be given 7 days before treatment with pemetrexed and continued until 21 days after discontinuation of pemetrexed to reduce the risk of hematologic and gastrointestinal toxicities.
  • Administer vitamin supplements. Administration of vitamin B12 intramuscular supplement one week before treatment with pemetrexed and every three cycles will reduce the risk of hematological and gastrointestinal toxicities.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Pemetrexed disodium2PKU919BA9150399-23-8NYDXNILOWQXUOF-GXKRWWSZSA-L
Pemetrexed disodium hemipentahydrateF4GSH45R4C357166-30-4ZCTCZKWJFTYNMZ-WKUCUCPSSA-J
Pemetrexed disodium heptahydrate9T47E4OM16357166-29-1QJVSMHJWAOSBMD-MYXYZBIASA-L
Pemetrexed ditromethamineHU11J9IK8F1645228-03-0HNJZWVKZQZMXHP-GXKRWWSZSA-N
Pemetrexed monohydrate236Y2F7D9JNot AvailableNBNBOZLBWLNZHB-ZOWNYOTGSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act PemetrexedPowder, for solutionIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act PemetrexedPowder, for solutionIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act PemetrexedPowder, for solutionIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
AlimtaPowder, for solutionIntravenousEli Lilly & Co. Ltd.2009-01-09Not applicableCanada flag
AlimtaInjection, powder, for solution500 mgIntravenousEli Lilly Nederland B.V.2016-09-08Not applicableEU flag
AlimtaInjection, powder, lyophilized, for solution500 mg/20mLIntravenousEli Lilly and Company2004-02-04Not applicableUS flag
AlimtaPowder, for solutionIntravenousEli Lilly & Co. Ltd.2004-08-03Not applicableCanada flag
AlimtaInjection, powder, lyophilized, for solution100 mg/4mLIntravenousEli Lilly and Company2007-09-07Not applicableUS flag
AlimtaInjection, powder, for solution100 mgIntravenousEli Lilly Nederland B.V.2016-09-08Not applicableEU flag
ArmisarteInjection, solution, concentrate25 mg/mlIntravenousActavis Group Ptc Ehf.2021-02-11Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Taro-pemetrexedPowder, for solutionIntravenousTaro Pharmaceuticals, Inc.Not applicableNot applicableCanada flag
Taro-pemetrexedPowder, for solutionIntravenousTaro Pharmaceuticals, Inc.2017-02-15Not applicableCanada flag
Taro-pemetrexedPowder, for solutionIntravenousTaro Pharmaceuticals, Inc.2018-10-18Not applicableCanada flag

Categories

ATC Codes
L01BA04 — Pemetrexed
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Glutamic acid and derivatives
Alternative Parents
N-acyl-alpha amino acids / Hippuric acids / Pyrrolo[2,3-d]pyrimidines / Benzoyl derivatives / Pyrimidones / Aminopyrimidines and derivatives / Substituted pyrroles / Dicarboxylic acids and derivatives / Vinylogous amides / Heteroaromatic compounds
show 9 more
Substituents
Amine / Amino acid / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Benzamide / Benzenoid / Benzoic acid or derivatives / Benzoyl / Carbonyl group
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
pyrrolopyrimidine, N-acyl-L-glutamic acid (CHEBI:63616)

Chemical Identifiers

UNII
04Q9AIZ7NO
CAS number
137281-23-3
InChI Key
WBXPDJSOTKVWSJ-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-{2-amino-4-oxo-1H,4H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)phenyl]formamido}pentanedioic acid
SMILES
NC1=NC(=O)C2=C(NC=C2CCC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N1

References

Synthesis Reference
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]
KEGG Drug
D07472
PubChem Compound
446556
PubChem Substance
46505640
ChemSpider
393879
BindingDB
50027656
RxNav
68446
ChEBI
63616
ChEMBL
CHEMBL225072
ZINC
ZINC000001540998
Therapeutic Targets Database
DCL000320
PharmGKB
PA10810
PDBe Ligand
LYA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pemetrexed
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
1ju6 / 1juj / 2x9g / 3k2h / 4fqs / 4kn2 / 4lvy / 6nnc / 6smw
FDA label
Download (233 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentLocally Advanced Malignant Neoplasm1
4CompletedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)3
4Not Yet RecruitingTreatmentAdvanced Non-squamous Non-small-cell Lung Cancer1
4RecruitingDiagnosticMesothelioma / Non-Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentAdvanced Non-squamous NSCLC1
4RecruitingTreatmentMesothelioma / Non-Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4RecruitingTreatmentPrimary Central Nervous System Lymphoma (PCNSL)1
4TerminatedTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
4Unknown StatusTreatmentAdenocarcinoma of the Lung2

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
  • Eli Lilly & Co.
Dosage Forms
FormRouteStrength
PowderIntravenous100 mg
Injection, powder, for solutionIntravenous151.7 mg
PowderIntravenous100 mg/1vial
PowderIntravenous500 mg
Solution10 ml
Solution50 ml
InjectionIntravenous100 mg
Injection, powder, lyophilized, for solutionIntravenous713 mg
Injection, powder, for solutionIntravenous100 mg
Injection, powder, for solutionIntravenous500 mg
PowderIntravenous500 mg/1vial
Injection, powder, for solution100 mg
Injection, powder, for solution500 mg
Injection, powder, lyophilized, for solutionIntravenous122.926 mg
Injection, powder, lyophilized, for solutionIntravenous100 mg
Injection, powder, lyophilized, for solutionIntravenous500 mg
Injection, powder, for solutionIntravenous25 mg/ml
Injection, powder, lyophilized, for solutionIntravenous110.29 mg
Injection, powder, lyophilized, for solutionIntravenous551.45 mg
Injection, solution, concentrateIntravenous25 mg/ml
Injection, powder, lyophilized, for solutionIntravenous100 mg/4mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/20mL
Injection, powder, for solutionIntravenous1000 mg
Injection, powder, for solutionParenteral100 mg
Injection, powder, for solutionParenteral1000 mg
Injection, powder, for solutionParenteral500 mg
Injection, powder, for solution1000 MG
Powder, for solutionIntravenous
Injection, powder, lyophilized, for solutionIntravenous120.82 mg
Injection, powder, lyophilized, for solutionIntravenous604.1 mg
Injection, powder, lyophilized, for solutionIntravenous110.28 mg
Injection, powder, lyophilized, for solutionIntravenous551.4 mg
Injection, powder, for solutionIntravenous554 mg
Injection, powder, lyophilized, for solutionIntravenous551.47 mg
Injection, solutionIntravenous100 MG
Injection, solutionIntravenous500 MG
Injection, solution, concentrateIntravenous
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)Region
US5217974No1993-06-082011-03-29US flag
CA2400155No2009-09-152021-02-12Canada flag
CA1340794No1999-10-192016-10-19Canada flag
US7772209Yes2010-08-102022-05-24US flag
US5344932Yes1994-09-062017-01-24US flag
US9604990No2015-10-282035-10-28US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0455 mg/mLALOGPS
logP0.11ALOGPS
logP1.2ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.39ChemAxon
pKa (Strongest Basic)2.43ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area186.97 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity109.45 m3·mol-1ChemAxon
Polarizability43.24 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
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
Uniprot Name
Thymidylate synthase
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
Humans
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
Uniprot Name
Bifunctional purine biosynthesis protein PURH
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
Humans
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 pre...
Gene Name
DHFR
Uniprot ID
P00374
Uniprot Name
Dihydrofolate reductase
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
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Phosphoribosylglycinamide formyltransferase activity
Specific Function
Not Available
Gene Name
GART
Uniprot ID
P22102
Uniprot Name
Trifunctional purine biosynthetic protein adenosine-3
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
Humans
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...
Gene Name
DCK
Uniprot ID
P27707
Uniprot Name
Deoxycytidine kinase
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
Humans
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...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
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]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Pemetrexed FDA Label [File]

Drug created on June 13, 2005 13:24 / Updated on February 24, 2021 19:34