Pemetrexed

Identification

Summary

Pemetrexed is a folate analog used to treat mesothelioma and non-small cell lung cancer.

Brand Names
Alimta, Ciambra, Pemfexy, Pemrydi Rtu
Generic Name
Pemetrexed
DrugBank Accession Number
DB00642
Background

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. Pemetrexed was first approved by the FDA in February 4, 2004.5

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

Pharmacology

Indication

Pemetrexed is indicated for the treatment of the following conditions:

Non-squamous non-small cell lung cancer (NSCLC)

  • in combination with pembrolizumab and platinum-based chemotherapy as initial treatment in metastatic disease where no EGFR or ALK genomic tumour aberrations exist 11
  • in combination with cisplatin as initial treatment for locally advanced or metastatic disease 11,14
  • as maintenance treatment for locally advanced or metastatic disease that has not progressed following four cycles of platinum-based chemotherapy 11,14
  • recurrent metastatic disease following prior chemotherapy 11
  • as monotherapy for the second-line treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer 14

Malignant pleural mesothelioma

  • in combination with cisplatin for the initial treatment of patients with malignant pleural mesothelioma.11,14 In the US, it is reserved for patients whose disease is unresectable or otherwise not candidates for curative surgery.11
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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofMetastatic cervical cancer••• •••••
Treatment ofMetastatic non-squamous non small cell lung cancer••••••••••••
Treatment ofMetastatic non-squamous non small cell lung cancer•••••••••••••• ••••• • •••••• •• •••••••••••••• •••••••••••••••••••••
Used in combination to treatMetastatic non-squamous non small cell lung cancerRegimen in combination with: Pembrolizumab (DB09037)•••••••••••••••••••••
Treatment ofOvarian cancer••• •••••
Associated Therapies
Contraindications & Blackbox Warnings
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Pharmacodynamics

Pemetrexed inhibited the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052) and showed synergistic effects when combined with cisplatin. Based on population pharmacodynamic analyses, the depth of the absolute neutrophil counts (ANC) nadir correlates with systemic exposure to pemetrexed and supplementation with folic acid and vitamin B12. There is no cumulative effect of pemetrexed exposure on ANC nadir over multiple treatment cycles.11

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.1,2,3,4,5,11

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

The pharmacokinetics of pemetrexed when pemetrexed was administered as a single agent in doses ranging from 0.2 to 838 mg/m2 infused over a 10-minute period have been evaluated in 426 cancer patients with a variety of solid tumors. Pemetrexed total systemic exposure (AUC) and maximum plasma concentration (Cmax) increased proportionally with the increase in dose. The pharmacokinetics of pemetrexed did not change over multiple treatment cycles.12

Volume of distribution

Pemetrexed has a steady-state volume of distribution of 16.1 liters.12

Protein binding

In vitro studies indicated that pemetrexed is 81% bound to plasma proteins.12

Metabolism

Pemetrexed is not metabolized to an appreciable extent by the liver.12,10

Route of elimination

Pemetrexed is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration. In vitro studies indicated that pemetrexed is a substrate of OAT3 (organic anion transporter 3), a transporter that is involved in the active secretion of pemetrexed.12

Half-life

The elimination half-life of pemetrexed is 3.5 hours in patients with normal renal function (creatinine clearance of 90 mL/min).12

Clearance

The total systemic clearance of pemetrexed is 91.8 mL/min in patients with normal renal function (creatinine clearance of 90 mL/min). As renal function decreases, the clearance of pemetrexed decreases, and exposure (AUC) of pemetrexed increases.12

Adverse Effects
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Toxicity

Not Available

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.
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 solution500 mg / vialIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act PemetrexedPowder, for solution100 mg / vialIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
Act PemetrexedPowder, for solution1000 mg / vialIntravenousActavis Pharma CompanyNot applicableNot applicableCanada flag
AlimtaInjection, powder, lyophilized, for solution100 mg/4mLIntravenousEli Lilly and Company2007-09-07Not applicableUS flag
AlimtaInjection, powder, for solution500 mgIntravenousEli Lilly Nederland B.V.2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PemetrexedInjection, powder, lyophilized, for solution1 g/40mLIntravenousAccord Healthcare Inc.2022-05-25Not applicableUS flag
PemetrexedInjection, powder, lyophilized, for solution500 mg/20mLIntravenousBluePoint Laboratories2022-06-24Not applicableUS flag
PemetrexedInjection, powder, lyophilized, for solution500 mg/50mLIntravenousMeitheal Pharmaceuticals Inc.2022-05-25Not applicableUS flag
PemetrexedInjection, powder, lyophilized, for solution1000 mg/40mLIntravenousZydus Lifesciences Limited2022-05-26Not applicableUS flag
PemetrexedInjection, powder, lyophilized, for solution500 mg/20mLIntravenousBluePoint Laboratories2022-06-27Not applicableUS 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)
Affected organisms
  • Humans and other mammals

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. [Article]
  2. Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic]. Bull Cancer. 2007;94 Spec No Actualites:S134-8. [Article]
  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. [Article]
  4. Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. [Article]
  5. Hazarika M, White RM, Johnson JR, Pazdur R: FDA drug approval summaries: pemetrexed (Alimta). Oncologist. 2004;9(5):482-8. doi: 10.1634/theoncologist.9-5-482. [Article]
  6. Sehouli J, Alvarez AM, Manouchehrpour S, Ghatage P, Szczylik C, Zimmermann A, Bauknecht T, Look KY, Oskay-Oezcelik G: A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer. Gynecol Oncol. 2012 Feb;124(2):205-9. doi: 10.1016/j.ygyno.2011.09.007. Epub 2011 Nov 1. [Article]
  7. Gbolahan OB, Porter RF, Salter JT, Yiannoutsos C, Burns M, Chiorean EG, Loehrer PJ Sr: A Phase II Study of Pemetrexed in Patients with Recurrent Thymoma and Thymic Carcinoma. J Thorac Oncol. 2018 Dec;13(12):1940-1948. doi: 10.1016/j.jtho.2018.07.094. Epub 2018 Aug 16. [Article]
  8. Choi YJ, Lee SH, Lee JL, Ahn JH, Lee KH, You D, Hong B, Hong JH, Ahn H: Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17). Br J Cancer. 2015 Jan 20;112(2):260-5. doi: 10.1038/bjc.2014.591. Epub 2014 Nov 27. [Article]
  9. He Y, Wang J, Xie S, Xue Q: Efficacy of Bevacizumab Combined with Pemetrexed in the Treatment of Recurrent and Metastatic Cervical Cancer. Front Surg. 2022 May 16;9:908101. doi: 10.3389/fsurg.2022.908101. eCollection 2022. [Article]
  10. Sorensen JB: Pharmacokinetic evaluation of pemetrexed. Expert Opin Drug Metab Toxicol. 2011 Jul;7(7):919-28. doi: 10.1517/17425255.2011.587411. Epub 2011 May 21. [Article]
  11. FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection [Link]
  12. FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]
  13. Pemetrexed MSDS [Link]
  14. EMA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Infusion [Link]
KEGG Drug
D07472
PubChem Compound
446556
PubChem Substance
46505640
ChemSpider
393879
BindingDB
18796
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
PDB Entries
1ju6 / 1juj / 2x9g / 3k2h / 4fqs / 4kn2 / 4lvy / 6nnc / 6smw / 7bc7
show 1 more
FDA label
Download (233 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedDiagnosticMesothelioma / Non-Small Cell Lung Cancer (NSCLC)1
4CompletedTreatmentLocally advanced Malignant Neoplasms1
4CompletedTreatmentNon-Small Cell Lung Cancer (NSCLC)4
4RecruitingTreatmentMetastatic Non-Small Cell Lung Cancer1
4RecruitingTreatmentNon-Small Cell Lung Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
  • Eli Lilly & Co.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous
Injection, powder, for solutionIntravenous100 MG
PowderIntravenous100 mg/1vial
SolutionParenteral500 mg
PowderIntravenous
Injection, powder, lyophilized, for solutionIntravenous500 mg/vial
SolutionIntravenous10 ml
InjectionIntravenous
Injection, powder, lyophilized, for solutionIntravenous713 mg
Injection, solution, concentrateIntravenous; Parenteral25 MG/ML
SolutionIntravenous500 mg
Injection, solution, concentrateIntravenous100 mg/1vial
PowderIntravenous500 mg/1vial
SolutionParenteral551.450 mg
Injection, powder, lyophilized, for solutionIntravenous50000000 mg
SolutionIntravenous604.12 mg
Injection, powder, for solution
SolutionIntravenous100.000 mg
SolutionIntravenous500.00 mg
Injection, powder, for solutionIntravenous500 mg
Injection, powder, for solutionIntravenous25 mg/ml
Injection, powder, for solutionIntravenous100 mg/vial
Injection, solution, concentrateIntravenous
InjectionIntravenous100 mg/10mL
InjectionIntravenous1000 mg/100mL
InjectionIntravenous500 mg/50mL
Injection, powder, lyophilized, for solutionIntravenous1 g/40mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/4.2mL
Injection, powder, lyophilized, for solutionIntravenous100 mg/4mL
Injection, powder, lyophilized, for solutionIntravenous1000 mg/40mL
Injection, powder, lyophilized, for solutionIntravenous25 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/20mL
Injection, powder, lyophilized, for solutionIntravenous500 mg/50mL
Injection, powder, lyophilized, for solutionIntravenous750 mg/30mL
Injection, powder, lyophilized, for solutionIntraventricular500 mg/50mL
Injection, solutionIntravenous100 mg/4mL
Injection, solutionIntravenous1000 mg/40mL
Injection, solutionIntravenous25 mg/1mL
Injection, solutionIntravenous500 mg/20mL
Injection, solutionIntravenous850 mg/34mL
Injection, solution, concentrateIntravenous1 g/40mL
Injection, solution, concentrateIntravenous100 mg/4mL
Injection, solution, concentrateIntravenous500 mg/20mL
Solution, concentrateIntravenous25 mg/1mL
Injection, powder, for solutionIntravenous1000 MG
Injection, powder, for solutionParenteral
Injection, powder, for solution100 MG
Injection, powder, for solution1000 MG
Injection, powder, for solution500 MG
Powder, for solutionIntravenous100 mg / vial
Powder, for solutionIntravenous1000 mg / vial
Powder, for solutionIntravenous500 mg / vial
Injection, solution, concentrateIntravenous25 MG/ML
SolutionIntravenous25 mg / mL
Injection, powder, lyophilized, for solutionIntravenous100 mg
Injection, powder, lyophilized, for solutionIntravenous500 mg
Injection, solutionIntravenous6 MG/ML
Injection, solutionIntravenous6.5 MG/ML
Injection, solutionIntravenous7 MG/ML
Injection, solutionIntravenous7.5 MG/ML
Injection, solutionIntravenous8 MG/ML
Injection, solutionIntravenous8.5 MG/ML
Injection, solutionIntravenous9 MG/ML
SolutionParenteral10 mg/ml
InjectionIntravenous25 mg/1mL
Injection, solution, concentrateIntravenous500 mg/1vial
PowderIntravenous100 mg
PowderIntravenous500 mg
InjectionParenteral25 mg/ml
SolutionIntravenous25.000 mg
Injection, powder, lyophilized, for solutionIntravenous100.00 mg
Injection, powder, for solutionIntravenous554 mg
Injection, powder, lyophilized, for solutionIntravenous500.00 mg
Injection, powder, for solutionParenteral500 mg
Injection, powder, lyophilized, for solutionIntravenous
Injection, solution, concentrateIntravenous100 mg
Injection, solution, concentrateIntravenous500 mg
Injection, powder, lyophilized, for solutionIntravenous10000000 mg
Injection, powder, lyophilized, for solutionIntravenous551.47 mg
Injection, solutionIntravenous
SolutionIntravenous500.0 mg
SolutionIntravenous110.300 mg
SolutionParenteral500.000 mg
Injection, solution, concentrateIntravenous25 mg/1ml
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
US9604990No2017-03-282035-10-28US flag
US11147817No2021-10-192035-03-26US flag
US11793813No2016-02-192036-02-19US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility89.4 g/l L43837
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/MSsplash10-001i-0090100000-724729441ab14c3cfd3b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-01ri-0309400000-a4c7f7d8cb53b6d5c546
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0090000000-b485b672058ceabcf394
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-1902000000-219bad7616bae40b15bf
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01q9-0890000000-7775592099d6b9d02582
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0udi-6931000000-9b97588f80e1b9083c41
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-207.1359384
predicted
DarkChem Lite v0.1.0
[M-H]-193.08038
predicted
DeepCCS 1.0 (2019)
[M+H]+206.5113384
predicted
DarkChem Lite v0.1.0
[M+H]+195.47595
predicted
DeepCCS 1.0 (2019)
[M+Na]+207.3412384
predicted
DarkChem Lite v0.1.0
[M+Na]+201.4423
predicted
DeepCCS 1.0 (2019)

Targets

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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. [Article]
  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. [Article]
  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. [Article]
  4. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
  5. Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
  8. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
  9. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
  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. [Article]
  11. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [Article]
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. [Article]
  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. [Article]
  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. [Article]
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. [Article]
  2. Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [Article]
  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. [Article]
  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. [Article]
  5. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  7. Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [Article]
  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. [Article]
  9. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
  10. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
  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. [Article]
  12. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [Article]
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. [Article]
  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. [Article]
  3. Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
  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. [Article]
  5. Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [Article]
  6. Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [Article]
  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. [Article]
  8. Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
  9. Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Muller C, Guzik P, Siwowska K, Cohrs S, Schmid RM, Schibli R: Combining Albumin-Binding Properties and Interaction with Pemetrexed to Improve the Tissue Distribution of Radiofolates. Molecules. 2018 Jun 16;23(6). pii: molecules23061465. doi: 10.3390/molecules23061465. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
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. FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]
  2. Pemetrexed FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Reduced folate carrier activity
Specific Function
Transporter for the intake of folate. Uptake of folate in human placental choriocarcinoma cells occurs by a novel mechanism called potocytosis which functionally couples three components, namely th...
Gene Name
SLC19A1
Uniprot ID
P41440
Uniprot Name
Folate transporter 1
Molecular Weight
64867.62 Da
References
  1. FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Methotrexate transporter activity
Specific Function
Has been shown to act both as an intestinal proton-coupled high-affinity folate transporter and as an intestinal heme transporter which mediates heme uptake from the gut lumen into duodenal epithel...
Gene Name
SLC46A1
Uniprot ID
Q96NT5
Uniprot Name
Proton-coupled folate transporter
Molecular Weight
49770.04 Da
References
  1. Giovannetti E, Zucali PA, Assaraf YG, Funel N, Gemelli M, Stark M, Thunnissen E, Hou Z, Muller IB, Struys EA, Perrino M, Jansen G, Matherly LH, Peters GJ: Role of proton-coupled folate transporter in pemetrexed resistance of mesothelioma: clinical evidence and new pharmacological tools. Ann Oncol. 2017 Nov 1;28(11):2725-2732. doi: 10.1093/annonc/mdx499. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Li L, Sham YY, Bikadi Z, Elmquist WF: pH-Dependent transport of pemetrexed by breast cancer resistance protein. Drug Metab Dispos. 2011 Sep;39(9):1478-85. doi: 10.1124/dmd.111.039370. Epub 2011 May 31. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Organic anion transmembrane transporter activity
Specific Function
Acts as a multispecific organic anion pump which can transport nucleotide analogs.
Gene Name
ABCC5
Uniprot ID
O15440
Uniprot Name
Multidrug resistance-associated protein 5
Molecular Weight
160658.8 Da
References
  1. Chen J, Wang Z, Gao S, Wu K, Bai F, Zhang Q, Wang H, Ye Q, Xu F, Sun H, Lu Y, Liu Y: Human drug efflux transporter ABCC5 confers acquired resistance to pemetrexed in breast cancer. Cancer Cell Int. 2021 Feb 25;21(1):136. doi: 10.1186/s12935-021-01842-x. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Kurata T, Iwamoto T, Kawahara Y, Okuda M: Characteristics of pemetrexed transport by renal basolateral organic anion transporter hOAT3. Drug Metab Pharmacokinet. 2014;29(2):148-53. doi: 10.2133/dmpk.dmpk-13-rg-042. Epub 2013 Sep 17. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48