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Identification
- Summary
Pemetrexed is a folate analog used to treat mesothelioma and non-small cell lung cancer.
- Brand Names
- Alimta, 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
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
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic cervical cancer ••• ••••• Treatment of Metastatic non-squamous non small cell lung cancer •••••••••••• Treatment of Metastatic non-squamous non small cell lung cancer •••••••••••• •• ••••• • •••••• •• •••••••••••••• •••••••••••• ••••••••• Used in combination to treat Metastatic non-squamous non small cell lung cancer Regimen in combination with: Pembrolizumab (DB09037) •••••••••••• ••••••••• Treatment of Ovarian cancer ••• ••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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 AThymidylate synthase inhibitorYeast ABifunctional purine biosynthesis protein ATIC 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. View sample adverse effects data in our new Data Library!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. - 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
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 1000 mg / vial Intravenous Actavis Pharma Company Not applicable Not applicable Canada 
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 Alimta Powder, for solution 500 mg / vial Intravenous Eli Lilly & Co. Ltd. 2004-08-03 2021-09-17 Canada Alimta Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Eli Lilly Nederland B.V. 2004-02-04 Not applicable US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Pemetrexed Injection, powder, lyophilized, for solution 750 mg/30mL Intravenous BluePoint Laboratories 2023-02-28 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 750 mg/30mL Intravenous Fresenius Kabi Italia S.R.L. 2022-05-25 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 750 mg/30mL Intravenous Meitheal Pharmaceuticals Inc. 2022-12-13 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 1 g/40mL Intravenous Accord Healthcare, S.L.U. 2022-05-25 Not applicable US Pemetrexed Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Apotex Corporation 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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Approved for Marketing Not Available Mesothelioma 1 somestatus stop reason just information to hide Not Available Completed Not Available Analgesia / Delirium / Immunotherapy / Non-Small Cell Lung Cancer (NSCLC) 1 somestatus stop reason just information to hide Not Available Completed Not Available Lung Neoplasm 1 somestatus stop reason just information to hide Not Available Completed Not Available Malignant Pleural Mesothelioma (MPM) / Non-Small Cell Lung Cancer (NSCLC) 1 somestatus stop reason just information to hide Not Available Completed Not Available Metastatic Lung Cancer / Non-Small Cell Lung Cancer (NSCLC) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Packagers
- Eli Lilly & Co.
- Dosage Forms
Form Route Strength Powder Intravenous Injection, powder, for solution Intravenous 100 MG Injection, powder, for solution Intravenous 151.7 mg Powder Intravenous 100 mg/1vial Solution Parenteral 500 mg Injection, powder, lyophilized, for solution Intravenous 500 mg/vial Solution Intravenous 10 ml Injection Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 713 mg Injection, solution, concentrate Intravenous; Parenteral 25 MG/ML Solution Intravenous 500 mg Injection, solution, concentrate Intravenous 100 mg/1vial Powder Intravenous 500 mg/1vial Solution Parenteral 551.450 mg Injection, powder, lyophilized, for solution Intravenous 50000000 mg Solution Intravenous 604.12 mg Solution Intravenous 100.000 mg Injection, powder, lyophilized, for solution Intravenous 122.926 mg Solution Intravenous 500.00 mg Injection, powder, for solution Intravenous 25 mg/ml Injection, powder, lyophilized, for solution Intravenous 110.29 mg Injection, powder, for solution Intravenous 100 mg/vial Injection, powder, lyophilized, for solution Intravenous 551.45 mg Injection, powder, for solution Intravenous 500 mg Injection, solution, concentrate Intravenous Injection Intravenous 100 mg/10mL Injection Intravenous 1000 mg/100mL Injection Intravenous 500 mg/50mL Injection, powder, for solution Intravenous 100 mg/1 Injection, powder, lyophilized, for solution Intravenous 1 g/40mL Injection, powder, lyophilized, for solution Intravenous 100 mg/10mL 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 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, powder, lyophilized, for solution Intravenous 120.82 mg Injection, powder, lyophilized, for solution Intravenous 604.1 mg Injection, solution, concentrate Intravenous 25 MG/ML Solution Intravenous 25 mg / mL Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 500 mg Injection, powder, for solution Injection, solution Intravenous 6 MG/ML Injection, solution Intravenous 6.5 MG/ML Injection, solution Intravenous 7 MG/ML Injection, solution Intravenous 7.5 MG/ML Injection, solution Intravenous 8 MG/ML Injection, solution Intravenous 8.5 MG/ML Injection, solution Intravenous 9 MG/ML Solution Parenteral 10 mg/ml Injection Intravenous 25 mg/1mL Injection, solution, concentrate Intravenous 500 mg/1vial Powder Intravenous 100 mg Powder Intravenous 500 mg Injection, powder, lyophilized, for solution Intravenous 110.28 mg Injection, powder, lyophilized, for solution Intravenous 551.4 mg Injection Parenteral 25 mg/ml Solution Intravenous 25.000 mg 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, for solution Parenteral 500 mg Injection, solution, concentrate Intravenous 100 mg Injection, solution, concentrate Intravenous 500 mg Injection, powder, lyophilized, for solution Intravenous 10000000 mg Injection, powder, lyophilized, for solution Intravenous 551.47 mg Injection, solution Intravenous 100 MG Injection, solution Intravenous 500 MG Solution Intravenous 500.0 mg Injection Parenteral 10 mg/ml Solution Intravenous 110.300 mg Solution Parenteral 500.000 mg 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 US11147817 No 2021-10-19 2035-03-26 US US11793813 No 2016-02-19 2036-02-19 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 splash10-001i-0090100000-724729441ab14c3cfd3b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-01ri-0309400000-a4c7f7d8cb53b6d5c546 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0090000000-b485b672058ceabcf394 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-1902000000-219bad7616bae40b15bf Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-01q9-0890000000-7775592099d6b9d02582 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-6931000000-9b97588f80e1b9083c41 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 207.1359384 predictedDarkChem Lite v0.1.0 [M-H]- 193.08038 predictedDeepCCS 1.0 (2019) [M+H]+ 206.5113384 predictedDarkChem Lite v0.1.0 [M+H]+ 195.47595 predictedDeepCCS 1.0 (2019) [M+Na]+ 207.3412384 predictedDarkChem Lite v0.1.0 [M+Na]+ 201.4423 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway
- Specific Function
- folic acid binding
- 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
- Yeast
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- FMN binding
- Gene Name
- TMP1
- Uniprot ID
- P12461
- Uniprot Name
- Thymidylate synthase
- Molecular Weight
- 35996.01 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:11948179, PubMed:14756554). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:10985775, PubMed:11948179, PubMed:9378707). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction (PubMed:10985775). Also catalyzes the cyclization of FAICAR to IMP (PubMed:11948179, PubMed:14756554). Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias (PubMed:10985775). Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571)
- Specific Function
- cadherin binding
- Gene Name
- ATIC
- Uniprot ID
- P31939
- Uniprot Name
- Bifunctional purine biosynthesis protein ATIC
- 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
- Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2
- Specific Function
- dihydrofolate reductase activity
- 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
- Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway
- Specific Function
- ATP binding
- 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
- Uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:10722669, PubMed:10755314, PubMed:12527552, PubMed:14759222, PubMed:15037197, PubMed:17379602, PubMed:21795683, PubMed:26406980, PubMed:27995448, PubMed:35790189, PubMed:8986748). Functions as a Na(+)-independent transporter (PubMed:8986748). Involved in the transport of nucleosides such as adenosine, guanosine, inosine, uridine, thymidine and cytidine (PubMed:10722669, PubMed:10755314, PubMed:12527552, PubMed:14759222, PubMed:15037197, PubMed:17379602, PubMed:26406980, PubMed:8986748). Also transports purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil) (PubMed:21795683, PubMed:27995448). Mediates basolateral nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis barrier (By similarity). Regulates inosine levels in brown adipocytes tissues (BAT) and extracellular inosine levels, which controls BAT-dependent energy expenditure (PubMed:35790189)
- Specific Function
- adenine transmembrane transporter activity
- 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
- Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine (PubMed:12808445, PubMed:18377927, PubMed:19159229, PubMed:1996353, PubMed:20614893, PubMed:20637175). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents (PubMed:12808445)
- Specific Function
- ATP binding
- 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
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- 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
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31126740, PubMed:31511694, PubMed:32276275, PubMed:7826387, PubMed:9041240). Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates (PubMed:22554803, PubMed:31126740, PubMed:31511694). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803). Also able to mediate the import of antifolate drug methotrexate (PubMed:22554803, PubMed:7615551, PubMed:7641195, PubMed:9767079). Also acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses (PubMed:31126740, PubMed:31511694, PubMed:36745868). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803)
- Specific Function
- 2',3'-cyclic GMP-AMP binding
- Gene Name
- SLC19A1
- Uniprot ID
- P41440
- Uniprot Name
- Reduced folate transporter
- 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
- Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:32893190). Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:32893190, PubMed:34040256). Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (PubMed:34040256). Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases (PubMed:18524888, PubMed:19762432, PubMed:22345511, PubMed:25608532, PubMed:28802835, PubMed:29326243, PubMed:34040256, PubMed:34619546). Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes (PubMed:19074442). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (PubMed:17156779). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (PubMed:32621820). Hence, participates in the trafficking of heme and increases intracellular iron content (PubMed:32621820)
- Specific Function
- folic acid binding
- 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
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- 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
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (PubMed:10893247, PubMed:12637526, PubMed:12695538, PubMed:15899835, PubMed:17229149, PubMed:25964343). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (PubMed:12695538). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated (PubMed:10840050, PubMed:12435799, PubMed:12695538, PubMed:15899835). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCC5
- Uniprot ID
- O15440
- Uniprot Name
- ATP-binding cassette sub-family C member 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
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- 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
- Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds (PubMed:10660625, PubMed:11907186, PubMed:15037815, PubMed:15102942, PubMed:15291761, PubMed:15576633, PubMed:17229912, PubMed:18501590, PubMed:26277985, PubMed:28027879). May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus (PubMed:12409283). Maybe also be involved in placental urate homeostasis (PubMed:17229912). Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates (PubMed:15037815, PubMed:17229912). Organic anion glutarate acts as conteranion for E1S renal uptake (PubMed:15037815, PubMed:17229912). Possible transport mode may also include DHEA-S/E1S exchange (PubMed:28027879). Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) (PubMed:17229912). Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion (PubMed:11907186). Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A (PubMed:10660625, PubMed:26277985). Mediates the unidirectional efflux of glutamate and aspartate (PubMed:28027879). Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S (PubMed:26277985)
- Specific Function
- organic anion transmembrane transporter activity
- 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 October 21, 2024 12:53