Identification
- Summary
Pemetrexed is a folate analog used to treat mesothelioma and non-small cell lung cancer.
- Brand Names
- Alimta, Ciambra, Pemfexy
- 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
Structure for Pemetrexed (DB00642)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
- Metastatic Cervical Cancer
- Metastatic Non-squamous Non Small Cell Lung Cancer
- Metastatic Ureter Urothelial Carcinoma
- Ovarian Cancer
- Locally advanced nonsquamous non-small cell lung cancer
- Recurrent, metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
- Unresectable Malignant Pleural Mesothelioma (MPM)
- Unresectable Thymoma
- Associated Therapies
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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
Target Actions Organism AThymidylate synthase inhibitorHumans ABifunctional purine biosynthesis protein PURH inhibitorHumans ADihydrofolate reductase inhibitorHumans ATrifunctional purine biosynthetic protein adenosine-3 inhibitorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Pemetrexed which could result in a higher serum level. Abametapir The serum concentration of Pemetrexed can be increased when it is combined with Abametapir. Abatacept The metabolism of Pemetrexed can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Pemetrexed. Abiraterone The serum concentration of Pemetrexed can be increased when it is combined with Abiraterone. Aceclofenac Aceclofenac may decrease the excretion rate of Pemetrexed which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Pemetrexed which could result in a higher serum level. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Pemetrexed. Acetaminophen Acetaminophen may decrease the excretion rate of Pemetrexed which could result in a higher serum level. Acetazolamide The therapeutic efficacy of Pemetrexed can be increased when used in combination with Acetazolamide. 
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- 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
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Pemetrexed disodium 2PKU919BA9 150399-23-8 NYDXNILOWQXUOF-GXKRWWSZSA-L Pemetrexed disodium hemipentahydrate F4GSH45R4C 357166-30-4 ZCTCZKWJFTYNMZ-WKUCUCPSSA-J Pemetrexed disodium heptahydrate 9T47E4OM16 357166-29-1 QJVSMHJWAOSBMD-MYXYZBIASA-L Pemetrexed ditromethamine HU11J9IK8F 1645228-03-0 HNJZWVKZQZMXHP-GXKRWWSZSA-N Pemetrexed monohydrate 236Y2F7D9J Not Available NBNBOZLBWLNZHB-ZOWNYOTGSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Pemetrexed Powder, for solution 500 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada 
Act Pemetrexed Powder, for solution 100 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada Act Pemetrexed Powder, for solution 1000 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada Alimta Injection, powder, for solution 500 mg Intravenous Eli Lilly Nederland B.V. 2016-09-08 Not applicable EU 
Alimta Powder, for solution 100 mg / vial Intravenous Eli Lilly & Co. Ltd. 2009-01-09 Not applicable Canada Alimta Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Eli Lilly and Company 2004-02-04 Not applicable US 
Alimta Powder, for solution 500 mg / vial Intravenous Eli Lilly & Co. Ltd. 2004-08-03 2021-09-17 Canada Alimta Injection, powder, for solution 100 mg Intravenous Eli Lilly Nederland B.V. 2016-09-08 Not applicable EU Alimta Injection, powder, lyophilized, for solution 100 mg/4mL Intravenous Eli Lilly and Company 2007-09-07 Not applicable US Armisarte Injection, solution, concentrate 25 mg/ml Intravenous Actavis Group Ptc Ehf. 2021-02-11 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Pemetrexed Injection, powder, lyophilized, for solution 100 mg/4mL Intravenous Eugia US LLC 2022-05-25 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 1 g/40mL Intravenous BluePoint Laboratories 2022-06-27 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 100 mg/4mL Intravenous Waverley Pharma Inc 2018-06-04 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Ingenus Pharmaceuticals, LLC 2022-05-24 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 100 mg/4mL Intravenous Zydus Pharmaceuticals USA Inc. 2022-05-26 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 100 mg/4.2mL Intravenous Athenex Pharmaceutical Division, Llc. 2022-05-25 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 1000 mg/40mL Intravenous Apotex Corp 2022-05-25 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 500 mg/50mL Intraventricular Baxter Healthcare Corporation 2022-08-18 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 1000 mg/40mL Intravenous BluePoint Laboratories 2023-02-28 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Fresenius Kabi USA, LLC 2022-05-25 Not applicable US
Categories
- ATC Codes
- L01BA04 — Pemetrexed
- Drug Categories
- Amino Acids
- Amino Acids, Acidic
- Amino Acids, Dicarboxylic
- Amino Acids, Peptides, and Proteins
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index
- Enzyme Inhibitors
- Folic Acid Analogues
- Folic Acid Antagonists
- Glutamates
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Nucleic Acid Synthesis Inhibitors
- OAT3/SLC22A8 Substrates
- OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index
- 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
- Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. [Article]
- Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic]. Bull Cancer. 2007;94 Spec No Actualites:S134-8. [Article]
- 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]
- Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection [Link]
- FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]
- Pemetrexed MSDS [Link]
- EMA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Infusion [Link]
- External Links
- KEGG Drug
- D07472
- PubChem Compound
- 446556
- PubChem Substance
- 46505640
- ChemSpider
- 393879
- BindingDB
- 18796
- 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
Phase Status Purpose Conditions Count 4 Completed Diagnostic Mesotheliomas / Non-Small Cell Lung Cancer (NSCLC) 1 4 Completed Treatment Locally advanced Malignant Neoplasms 1 4 Completed Treatment Non-Small Cell Lung Cancer (NSCLC) 4 4 Recruiting Treatment Non-Small Cell Lung Cancer (NSCLC) 1 4 Recruiting Treatment Primary Central Nervous System Lymphoma 1 4 Terminated Treatment Mesotheliomas / Non-Small Cell Lung Cancer (NSCLC) 1 4 Terminated Treatment Non-Small Cell Lung Carcinoma 1 4 Unknown Status Treatment Adenocarcinoma of the Lung 2 4 Unknown Status Treatment Adenocarcinomas / EGFR Positive Non-small Cell Lung Cancer 2 4 Unknown Status Treatment Advanced Non Squamous NSCLC 1
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Packagers
- Eli Lilly & Co.
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous Injection, powder, for solution Intravenous 100 MG Injection, powder, for solution Parenteral 500 mg Powder Intravenous 100 mg/1vial Solution Parenteral 500 mg Powder Intravenous Injection, powder, lyophilized, for solution Intravenous 500 mg/vial Solution Intravenous 10 ml Injection Intravenous Injection, powder, lyophilized, for solution Intravenous 713 mg Injection, solution, concentrate Intravenous; Parenteral 25 MG/ML Injection, solution, concentrate Intravenous 100 mg/1vial Powder Intravenous 500 mg/1vial Injection, powder, for solution Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, powder, for solution Intravenous 500 mg Injection, powder, for solution Intravenous 25 mg/ml Injection, powder, lyophilized, for solution Intravenous 500 mg Injection, powder, for solution Intravenous 100 mg/vial Injection, solution, concentrate Intravenous Injection, powder, lyophilized, for solution Intravenous 1 g/40mL Injection, powder, lyophilized, for solution Intravenous 100 mg/4mL Injection, powder, lyophilized, for solution Intravenous 100 mg/4.2mL Injection, powder, lyophilized, for solution Intravenous 100 mg/10mL Injection, powder, lyophilized, for solution Intravenous 1000 mg/40mL Injection, powder, lyophilized, for solution Intravenous 25 mg/1mL Injection, powder, lyophilized, for solution Intravenous 500 mg/50mL Injection, powder, lyophilized, for solution Intravenous 500 mg/20mL Injection, powder, lyophilized, for solution Intravenous 750 mg/30mL Injection, powder, lyophilized, for solution Intraventricular 500 mg/50mL Injection, solution Intravenous 100 mg/4mL Injection, solution Intravenous 1000 mg/40mL Injection, solution Intravenous 25 mg/1mL Injection, solution Intravenous 500 mg/20mL Injection, solution Intravenous 850 mg/34mL Injection, solution, concentrate Intravenous 1 g/40mL Injection, solution, concentrate Intravenous 100 mg/4mL Injection, solution, concentrate Intravenous 500 mg/20mL Solution, concentrate Intravenous 25 mg/1mL Injection, powder, for solution Intravenous 1000 MG Injection, powder, for solution Parenteral Injection, powder, for solution 100 MG Injection, powder, for solution 1000 MG Injection, powder, for solution 500 MG Powder, for solution Intravenous 100 mg / vial Powder, for solution Intravenous 1000 mg / vial Powder, for solution Intravenous 500 mg / vial Injection, solution, concentrate Intravenous 25 MG/ML Solution Intravenous 25 mg / mL Injection Intravenous 25 mg/1mL Injection, solution, concentrate Intravenous 500 mg/1vial Powder Intravenous 100 mg Powder Intravenous 500 mg Injection Parenteral 25 mg/ml Injection, powder, lyophilized, for solution Intravenous 100.00 mg Injection, powder, for solution Intravenous 554 mg Injection, powder, lyophilized, for solution Intravenous 500.00 mg Injection, powder, lyophilized, for solution Intravenous Injection, solution, concentrate Intravenous 100 mg Injection, solution, concentrate Intravenous 500 mg Injection, powder, lyophilized, for solution Intravenous 551.47 mg Injection, solution Intravenous Injection, solution, concentrate Intravenous 25 mg/1ml - Prices
Unit description Cost Unit Alimta 500 mg Solution Vial 3154.94USD vial Alimta 500 mg vial 3033.6USD vial Alimta 100 mg vial 606.72USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5217974 No 1993-06-08 2011-03-29 US CA2400155 No 2009-09-15 2021-02-12 Canada CA1340794 No 1999-10-19 2016-10-19 Canada US7772209 Yes 2010-08-10 2022-05-24 US US5344932 Yes 1994-09-06 2017-01-24 US US9604990 No 2017-03-28 2035-10-28 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility 89.4 g/l L43837 - Predicted Properties
Property Value Source Water Solubility 0.0455 mg/mL ALOGPS logP 0.11 ALOGPS logP 1.2 Chemaxon logS -4 ALOGPS pKa (Strongest Acidic) 3.39 Chemaxon pKa (Strongest Basic) 2.43 Chemaxon Physiological Charge -2 Chemaxon Hydrogen Acceptor Count 9 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 186.97 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 109.45 m3·mol-1 Chemaxon Polarizability 43.24 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.6997 Blood Brain Barrier + 0.7542 Caco-2 permeable - 0.819 P-glycoprotein substrate Substrate 0.5 P-glycoprotein inhibitor I Non-inhibitor 0.9729 P-glycoprotein inhibitor II Non-inhibitor 0.9825 Renal organic cation transporter Non-inhibitor 0.8923 CYP450 2C9 substrate Non-substrate 0.7547 CYP450 2D6 substrate Non-substrate 0.8204 CYP450 3A4 substrate Non-substrate 0.6051 CYP450 1A2 substrate Non-inhibitor 0.912 CYP450 2C9 inhibitor Non-inhibitor 0.8938 CYP450 2D6 inhibitor Non-inhibitor 0.9117 CYP450 2C19 inhibitor Non-inhibitor 0.8844 CYP450 3A4 inhibitor Non-inhibitor 0.8253 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9508 Ames test Non AMES toxic 0.8528 Carcinogenicity Non-carcinogens 0.964 Biodegradation Not ready biodegradable 0.8296 Rat acute toxicity 2.5023 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9624 hERG inhibition (predictor II) Non-inhibitor 0.8718
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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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
- Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [Article]
- 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]
- 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]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
- Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
- 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]
- 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
- Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [Article]
- 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]
- 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
- 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]
- Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [Article]
- 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]
- 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]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [Article]
- 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]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
- 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]
- 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
- 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]
- 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]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [Article]
- 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]
- Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [Article]
- Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [Article]
- 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]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [Article]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [Article]
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- FDA Approved Drug Products: ALIMTA (pemetrexed) Intravenous Injection (Nov 2022) [Link]
Drug created at June 13, 2005 13:24 / Updated at March 21, 2023 17:58