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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Pemetrexed
- Accession Number
- DB00642 (APRD00573, EXPT02075)
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Description
Pemetrexed (brand name Alimta) is a chemotherapy drug manufactured and marketed by Eli Lilly and Company. Its indications are the treatment of pleural mesothelioma as well as non-small cell lung cancer.
- Structure
Structure for DB00642 (Pemetrexed)
- Synonyms
- Not Available
- External IDs
- LY-231514 / LY231514 / NSC-698037
- 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 monohydrate 236Y2F7D9J Not Available NBNBOZLBWLNZHB-ZOWNYOTGSA-N - Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Act Pemetrexed Powder, for solution 1000 mg Intravenous Actavis Pharma Company Not applicable Not applicable Canada 
Act Pemetrexed Powder, for solution 500 mg Intravenous Actavis Pharma Company Not applicable Not applicable Canada Act Pemetrexed Powder, for solution 100 mg Intravenous Actavis Pharma Company Not applicable Not applicable Canada Alimta Injection, powder, lyophilized, for solution 500 mg/20mL Intravenous Eli Lilly & Co. Ltd. 2004-02-04 Not applicable US 
Alimta Powder, for solution 500 mg Intravenous Eli Lilly & Co. Ltd. 2004-08-03 Not applicable Canada Alimta Injection, powder, for solution 100 mg Intravenous Eli Lilly Nederland B.V. 2004-09-20 Not applicable EU 
Alimta Injection, powder, for solution 500 mg Intravenous Eli Lilly Nederland B.V. 2004-09-20 Not applicable EU Alimta Injection, powder, lyophilized, for solution 100 mg/4mL Intravenous Eli Lilly & Co. Ltd. 2007-09-07 Not applicable US Alimta Powder, for solution 100 mg Intravenous Eli Lilly & Co. Ltd. 2009-01-09 Not applicable Canada Pemetrexed Powder, for solution 500 mg Intravenous Apotex Corporation Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Ciambra Injection, powder, for solution 500 mg Intravenous Menarini International Operations Luxembourg S.A. 2015-12-02 Not applicable EU Ciambra Injection, powder, for solution 100 mg Intravenous Menarini International Operations Luxembourg S.A. 2015-12-02 Not applicable EU Pemetrexed Accord Injection, powder, for solution 500 mg Intravenous Accord Healthcare Limited 2016-01-18 Not applicable EU Pemetrexed Accord Injection, powder, for solution 100 mg Intravenous Accord Healthcare Limited 2016-01-18 Not applicable EU Pemetrexed Accord Injection, powder, for solution 1000 mg Intravenous Accord Healthcare Limited 2016-01-18 Not applicable EU Pemetrexed Hospira Injection, powder, for solution 500 mg Intravenous Hospira, Inc. 2015-11-20 Not applicable EU Pemetrexed Hospira Injection, powder, for solution 100 mg Intravenous Hospira, Inc. 2015-11-20 Not applicable EU Pemetrexed Hospira Injection, powder, for solution 1000 mg Intravenous Hospira, Inc. 2015-11-20 Not applicable EU Pemetrexed Lilly Injection, powder, for solution 500 mg Intravenous Eli Lilly Netherlands 2015-09-14 Not applicable EU Pemetrexed Lilly Injection, powder, for solution 100 mg Intravenous Eli Lilly Netherlands 2015-09-14 Not applicable EU - 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
- Drugs for Obstructive Airway Diseases
- Enzyme Inhibitors
- Folate Analog Metabolic Inhibitor
- Folic Acid Analogues
- Folic Acid Antagonists
- Glutamates
- Guanine
- Immunosuppressive Agents
- Myelosuppressive Agents
- Nucleic Acid Synthesis Inhibitors
- Purines
- Purinones
- Xanthine derivatives
- UNII
- 04Q9AIZ7NO
- CAS number
- 137281-23-3
- Weight
- Average: 427.4106
Monoisotopic: 427.149183429 - Chemical Formula
- C20H21N5O6
- 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-{4-hydroxy-2-imino-1H,2H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}ethyl)phenyl]formamido}pentanedioic acid
- SMILES
- [H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(CCC2=CNC3=C2C(O)=NC(=N)N3)C=C1)C(O)=O
Pharmacology
- Indication
Used in combination with cisplatin for the treatment of malignant pleural mesothelioma in adults whose disease is unresectable or who otherwise are not candidates for potentially curative surgery. Also used as a monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy
- Associated Conditions
- Pharmacodynamics
Preclinical studies have shown that pemetrexed inhibits the in vitro growth of mesothelioma cell lines (MSTO-211H, NCI-H2052). Studies with the MSTO-211H mesothelioma cell line showed synergistic effects when pemetrexed was combined concurrently with cisplatin.
- Mechanism of action
Pemetrexed is an antifolate containing the pyrrolopyrimidine-based nucleus that exerts its antineoplastic activity by disrupting folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), all folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Polyglutamation is a time- and concentration-dependent process that occurs in tumor cells and, to a lesser extent, in normal tissues. Polyglutamated metabolites have an increased intracellular half-life resulting in prolonged drug action in malignant cells.
Target Actions Organism AThymidylate synthase inhibitorHuman ABifunctional purine biosynthesis protein PURH inhibitorHuman ADihydrofolate reductase inhibitorHuman ATrifunctional purine biosynthetic protein adenosine-3 inhibitorHuman - Absorption
- Not Available
- Volume of distribution
- 16.1 L
- Protein binding
81%
- Metabolism
Metabolized by Cytochrome P450 Enzymes
- Route of elimination
Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70% to 90% of the dose recovered unchanged within the first 24 hours following administration.
- Half life
3.5 hours
- Clearance
- 91.8 mL/min [Cancer patients with normal renal function receiving 0.2 to 838 mg/m2 infusion over a 10-minute period]
- Toxicity
- Not Available
- Affected organisms
- Humans and other mammals
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Acetyldigitoxin Acetyldigitoxin may decrease the cardiotoxic activities of Pemetrexed. Approved Acetyldigoxin Acetyldigoxin may decrease the cardiotoxic activities of Pemetrexed. Experimental Adalimumab The serum concentration of Pemetrexed can be decreased when it is combined with Adalimumab. Approved Adenosine The therapeutic efficacy of Adenosine can be decreased when used in combination with Pemetrexed. Approved, Investigational Aldesleukin The risk or severity of adverse effects can be increased when Pemetrexed is combined with Aldesleukin. Approved Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Pemetrexed. Approved Ancestim The risk or severity of cytotoxicity can be increased when Ancestim is combined with Pemetrexed. Approved, Investigational, Withdrawn Anthrax immune globulin human The risk or severity of adverse effects can be increased when Pemetrexed is combined with Anthrax immune globulin human. Approved Bacillus calmette-guerin substrain connaught live antigen The risk or severity of adverse effects can be increased when Pemetrexed is combined with Bacillus calmette-guerin substrain connaught live antigen. Approved, Investigational Bacillus calmette-guerin substrain tice live antigen The risk or severity of adverse effects can be increased when Pemetrexed is combined with Bacillus calmette-guerin substrain tice live antigen. Approved BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Pemetrexed. Investigational Beclomethasone dipropionate The risk or severity of adverse effects can be increased when Pemetrexed is combined with Beclomethasone dipropionate. Approved, Investigational Benzphetamine The risk or severity of adverse effects can be increased when Benzphetamine is combined with Pemetrexed. Approved, Illicit Bevacizumab Bevacizumab may increase the cardiotoxic activities of Pemetrexed. Approved, Investigational Budesonide The risk or severity of adverse effects can be increased when Pemetrexed is combined with Budesonide. Approved Cabazitaxel The risk or severity of adverse effects can be increased when Cabazitaxel is combined with Pemetrexed. Approved Carbamazepine The serum concentration of Pemetrexed can be decreased when it is combined with Carbamazepine. Approved, Investigational Cimetidine The metabolism of Pemetrexed can be decreased when combined with Cimetidine. Approved, Investigational Ciprofloxacin The serum concentration of Pemetrexed can be increased when it is combined with Ciprofloxacin. Approved, Investigational Clostridium tetani toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pemetrexed is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated). Approved Clozapine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Clozapine. Approved Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pemetrexed is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). Approved Cyclophosphamide Cyclophosphamide may increase the cardiotoxic activities of Pemetrexed. Approved, Investigational Cyclosporine The risk or severity of adverse effects can be increased when Cyclosporine is combined with Pemetrexed. Approved, Investigational, Vet Approved Cymarin Cymarin may decrease the cardiotoxic activities of Pemetrexed. Experimental Denosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Pemetrexed. Approved Deslanoside Deslanoside may decrease the cardiotoxic activities of Pemetrexed. Approved Dexamethasone The risk or severity of adverse effects can be increased when Pemetrexed is combined with Dexamethasone. Approved, Investigational, Vet Approved Diclofenac The serum concentration of Pemetrexed can be increased when it is combined with Diclofenac. Approved, Vet Approved Diethylpropion The risk or severity of adverse effects can be increased when Diethylpropion is combined with Pemetrexed. Approved, Illicit Digitoxin Digitoxin may decrease the cardiotoxic activities of Pemetrexed. Approved, Investigational Digoxin Digoxin may decrease the cardiotoxic activities of Pemetrexed. Approved Digoxin Immune Fab (Ovine) Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Pemetrexed. Approved Docetaxel The risk or severity of adverse effects can be increased when Docetaxel is combined with Pemetrexed. Approved, Investigational Estradiol The serum concentration of Pemetrexed can be increased when it is combined with Estradiol. Approved, Investigational, Vet Approved Etanercept The risk or severity of adverse effects can be increased when Etanercept is combined with Pemetrexed. Approved, Investigational Ethinyl Estradiol The serum concentration of Pemetrexed can be increased when it is combined with Ethinyl Estradiol. Approved Ethosuximide Ethosuximide may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved Everolimus The risk or severity of adverse effects can be increased when Everolimus is combined with Pemetrexed. Approved Fingolimod Pemetrexed may increase the immunosuppressive activities of Fingolimod. Approved, Investigational Flunarizine Flunarizine may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved Fluticasone propionate The risk or severity of adverse effects can be increased when Pemetrexed is combined with Fluticasone propionate. Approved Fluvoxamine The metabolism of Pemetrexed can be decreased when combined with Fluvoxamine. Approved, Investigational G17DT The risk or severity of adverse effects can be increased when Pemetrexed is combined with G17DT. Investigational Gabapentin Gabapentin may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational Gemcitabine The risk or severity of adverse effects can be increased when Gemcitabine is combined with Pemetrexed. Approved Gemtuzumab ozogamicin The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Pemetrexed. Approved, Investigational GI-5005 The risk or severity of adverse effects can be increased when Pemetrexed is combined with GI-5005. Investigational Gitoformate Gitoformate may decrease the cardiotoxic activities of Pemetrexed. Experimental Hepatitis A Vaccine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hepatitis A Vaccine. Approved Hepatitis B Vaccine (Recombinant) The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hepatitis B Vaccine (Recombinant). Approved, Withdrawn Human rabies virus immune globulin The risk or severity of adverse effects can be increased when Pemetrexed is combined with Human rabies virus immune globulin. Approved Hydrocortisone The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hydrocortisone. Approved, Vet Approved Hydrocortisone acetate The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hydrocortisone acetate. Approved, Vet Approved Hydrocortisone butyrate The risk or severity of adverse effects can be increased when Pemetrexed is combined with Hydrocortisone butyrate. Approved, Vet Approved INGN 201 The risk or severity of adverse effects can be increased when Pemetrexed is combined with INGN 201. Investigational INGN 225 The risk or severity of adverse effects can be increased when Pemetrexed is combined with INGN 225. Investigational Interferon alfa-n3 The risk or severity of adverse effects can be increased when Pemetrexed is combined with Interferon alfa-n3. Approved, Investigational Interferon beta-1a The metabolism of Pemetrexed can be decreased when combined with Interferon beta-1a. Approved, Investigational Interferon gamma-1b The metabolism of Pemetrexed can be decreased when combined with Interferon gamma-1b. Approved, Investigational Irinotecan The risk or severity of adverse effects can be increased when Pemetrexed is combined with Irinotecan. Approved, Investigational Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated) The risk or severity of adverse effects can be increased when Pemetrexed is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated). Approved Ketorolac The serum concentration of Pemetrexed can be increased when it is combined with Ketorolac. Approved Labetalol The risk or severity of adverse effects can be increased when Labetalol is combined with Pemetrexed. Approved Lamotrigine Lamotrigine may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational Lanatoside C Lanatoside C may decrease the cardiotoxic activities of Pemetrexed. Experimental Leflunomide The risk or severity of adverse effects can be increased when Pemetrexed is combined with Leflunomide. Approved, Investigational Levetiracetam Levetiracetam may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational Lipegfilgrastim Pemetrexed may increase the myelosuppressive activities of Lipegfilgrastim. Approved, Investigational Magnesium sulfate Magnesium sulfate may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational, Vet Approved Metamizole The risk or severity of myelosuppression can be increased when Metamizole is combined with Pemetrexed. Approved, Investigational, Withdrawn Methimazole The risk or severity of adverse effects can be increased when Pemetrexed is combined with Methimazole. Approved Methsuximide Methsuximide may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved Methylprednisolone The risk or severity of adverse effects can be increased when Pemetrexed is combined with Methylprednisolone. Approved, Vet Approved Metildigoxin Metildigoxin may decrease the cardiotoxic activities of Pemetrexed. Experimental Metoprolol The risk or severity of adverse effects can be increased when Metoprolol is combined with Pemetrexed. Approved, Investigational Moxifloxacin The metabolism of Pemetrexed can be decreased when combined with Moxifloxacin. Approved, Investigational Naproxen The serum concentration of Pemetrexed can be increased when it is combined with Naproxen. Approved, Vet Approved Natalizumab The risk or severity of adverse effects can be increased when Pemetrexed is combined with Natalizumab. Approved, Investigational Nylidrin The risk or severity of adverse effects can be increased when Nylidrin is combined with Pemetrexed. Approved Nystatin The metabolism of Pemetrexed can be decreased when combined with Nystatin. Approved, Vet Approved Ocrelizumab Ocrelizumab may increase the immunosuppressive activities of Pemetrexed. Approved, Investigational Oleandrin Oleandrin may decrease the cardiotoxic activities of Pemetrexed. Experimental, Investigational Ouabain Ouabain may decrease the cardiotoxic activities of Pemetrexed. Approved Oxymetazoline The risk or severity of adverse effects can be increased when Oxymetazoline is combined with Pemetrexed. Approved, Investigational Palifermin The therapeutic efficacy of Palifermin can be decreased when used in combination with Pemetrexed. Approved Pegaspargase The risk or severity of adverse effects can be increased when Pegaspargase is combined with Pemetrexed. Approved, Investigational Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Pemetrexed is combined with Peginterferon alfa-2a. Approved, Investigational Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Pemetrexed is combined with Peginterferon alfa-2b. Approved Peruvoside Peruvoside may decrease the cardiotoxic activities of Pemetrexed. Experimental Phenobarbital The serum concentration of Pemetrexed can be decreased when it is combined with Phenobarbital. Approved, Investigational Phenylephrine The risk or severity of adverse effects can be increased when Phenylephrine is combined with Pemetrexed. Approved Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Pemetrexed. Approved, Investigational Prednisolone The risk or severity of adverse effects can be increased when Pemetrexed is combined with Prednisolone. Approved, Vet Approved Pregabalin Pregabalin may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Illicit, Investigational Propafenone The serum concentration of Pemetrexed can be increased when it is combined with Propafenone. Approved Propranolol The risk or severity of adverse effects can be increased when Propranolol is combined with Pemetrexed. Approved, Investigational Proscillaridin Proscillaridin may decrease the cardiotoxic activities of Pemetrexed. Experimental Pseudoephedrine The risk or severity of adverse effects can be increased when Pseudoephedrine is combined with Pemetrexed. Approved Rabies virus inactivated antigen, A The risk or severity of adverse effects can be increased when Pemetrexed is combined with Rabies virus inactivated antigen, A. Approved, Investigational Rabies virus inactivated antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Pemetrexed. Approved, Investigational Rindopepimut The risk or severity of adverse effects can be increased when Pemetrexed is combined with Rindopepimut. Investigational Roflumilast Roflumilast may increase the immunosuppressive activities of Pemetrexed. Approved Rotavirus Vaccine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Rotavirus Vaccine. Approved Rubella virus vaccine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Rubella virus vaccine. Approved, Investigational Salicylic acid The serum concentration of Pemetrexed can be increased when it is combined with Salicylic acid. Approved, Investigational, Vet Approved Salmonella typhi ty2 vi polysaccharide antigen The risk or severity of adverse effects can be increased when Pemetrexed is combined with Salmonella typhi ty2 vi polysaccharide antigen. Approved Salmonella typhi Ty21a live antigen The risk or severity of adverse effects can be increased when Pemetrexed is combined with Salmonella typhi ty21a live antigen. Approved SRP 299 The risk or severity of adverse effects can be increased when Pemetrexed is combined with SRP 299. Investigational Sulfasalazine The serum concentration of Pemetrexed can be increased when it is combined with Sulfasalazine. Approved Sulindac The serum concentration of Pemetrexed can be increased when it is combined with Sulindac. Approved, Investigational Tacrolimus Tacrolimus may increase the immunosuppressive activities of Pemetrexed. Approved, Investigational Tecemotide The risk or severity of adverse effects can be increased when Pemetrexed is combined with Tecemotide. Investigational Tetrandrine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Tetrandrine. Experimental TG4010 The risk or severity of adverse effects can be increased when Pemetrexed is combined with TG4010. Investigational Tofacitinib Pemetrexed may increase the immunosuppressive activities of Tofacitinib. Approved, Investigational Topiramate Topiramate may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved Trastuzumab Trastuzumab may increase the cardiotoxic activities of Pemetrexed. Approved, Investigational Trimethadione Trimethadione may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved Trolamine salicylate The serum concentration of Pemetrexed can be increased when it is combined with Trolamine salicylate. Approved Typhoid Vaccine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Typhoid Vaccine. Approved Valproic Acid Valproic Acid may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational Varicella Zoster Vaccine (Live/Attenuated) The risk or severity of adverse effects can be increased when Pemetrexed is combined with Varicella Zoster Vaccine (Live/Attenuated). Approved Vinpocetine Vinpocetine may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Investigational Yellow Fever Vaccine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Yellow Fever Vaccine. Approved, Investigational Zidovudine The risk or severity of adverse effects can be increased when Pemetrexed is combined with Zidovudine. Approved Zonisamide Zonisamide may increase the excretion rate of Pemetrexed which could result in a lower serum level and potentially a reduction in efficacy. Approved, Investigational - Food Interactions
- Not Available
References
- Synthesis Reference
- US5344932
- General References
- Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. [PubMed:16291410]
- Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic]. Bull Cancer. 2007;94 Spec No Actualites:S134-8. [PubMed:17845983]
- Fuld AD, Dragnev KH, Rigas JR: Pemetrexed in advanced non-small-cell lung cancer. Expert Opin Pharmacother. 2010 Jun;11(8):1387-402. doi: 10.1517/14656566.2010.482560. [PubMed:20446853]
- Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. [PubMed:12722874]
- External Links
- KEGG Drug
- D07472
- PubChem Compound
- 446556
- PubChem Substance
- 46505640
- ChemSpider
- 393879
- BindingDB
- 18796
- ChEBI
- 63616
- ChEMBL
- CHEMBL225072
- Therapeutic Targets Database
- DCL000320
- PharmGKB
- PA10810
- HET
- LYA
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pemetrexed
- ATC Codes
- R03DA20 — Combinations of xanthines
- R03DA — Xanthines
- R03D — OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R03 — DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
- R — RESPIRATORY SYSTEM
- AHFS Codes
- 10:00.00 — Antineoplastic Agents
- PDB Entries
- 1ju6 / 1juj / 2x9g / 3k2h / 4fqs / 4kn2 / 4lvy
- FDA label
- Download (233 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Eli lilly and co
- Packagers
- Eli Lilly & Co.
- Dosage forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 100 mg/4mL Injection, powder, lyophilized, for solution Intravenous 500 mg/20mL Powder, for solution Intravenous 100 mg Powder, for solution Intravenous 500 mg Injection, powder, for solution Intravenous 100 mg Injection, powder, for solution Intravenous 500 mg Injection, powder, for solution Intravenous 1000 mg Powder, for solution Intravenous 1000 mg - 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) US5217974 No 1994-03-29 2011-03-29 US CA2400155 No 2009-09-15 2021-02-12 Canada CA1340794 No 1999-10-19 2016-10-19 Canada US7772209 Yes 2002-05-24 2022-05-24 US US5344932 Yes 1997-01-24 2017-01-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP -1.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0905 mg/mL ALOGPS logP -0.19 ALOGPS logP -0.22 ChemAxon logS -3.7 ALOGPS pKa (Strongest Acidic) 2.72 ChemAxon pKa (Strongest Basic) 20.82 ChemAxon Physiological Charge -2 ChemAxon Hydrogen Acceptor Count 9 ChemAxon Hydrogen Donor Count 7 ChemAxon Polar Surface Area 187.96 Å2 ChemAxon Rotatable Bond Count 9 ChemAxon Refractivity 120.46 m3·mol-1 ChemAxon Polarizability 43.28 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
Taxonomy
- 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
- Glutamic acid or derivatives / Hippuric acid or derivatives / Hippuric acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Pyrrolopyrimidine / Benzamide / Pyrrolo[2,3-d]pyrimidine / Benzoic acid or derivatives / Benzoyl show 27 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- pyrrolopyrimidine, N-acyl-L-glutamic acid (CHEBI:63616)
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Thymidylate synthase activity
- Specific Function
- Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
- Gene Name
- TYMS
- Uniprot ID
- P04818
- 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. [PubMed:11252887]
- Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555]
- Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712]
- Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [PubMed:11763166]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Schultz RM, Dempsey JA: Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Anticancer Res. 2001 Sep-Oct;21(5):3209-14. [PubMed:11848474]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699]
- Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320]
- Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Protein homodimerization activity
- Specific Function
- Bifunctional enzyme that catalyzes 2 steps in purine biosynthesis.Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).
- Gene Name
- ATIC
- Uniprot ID
- P31939
- 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. [PubMed:12571811]
- Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555]
- Racanelli AC, Rothbart SB, Heyer CL, Moran RG: Therapeutics by cytotoxic metabolite accumulation: pemetrexed causes ZMP accumulation, AMPK activation, and mammalian target of rapamycin inhibition. Cancer Res. 2009 Jul 1;69(13):5467-74. doi: 10.1158/0008-5472.CAN-08-4979. Epub 2009 Jun 23. [PubMed:19549896]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Nadph binding
- Specific Function
- Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA 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. [PubMed:11524555]
- Norman P: Pemetrexed disodium (Eli Lilly). Curr Opin Investig Drugs. 2001 Nov;2(11):1611-22. [PubMed:11763166]
- Mauritz R, Peters GJ, Priest DG, Assaraf YG, Drori S, Kathmann I, Noordhuis P, Bunni MA, Rosowsky A, Schornagel JH, Pinedo HM, Jansen G: Multiple mechanisms of resistance to methotrexate and novel antifolates in human CCRF-CEM leukemia cells and their implications for folate homeostasis. Biochem Pharmacol. 2002 Jan 15;63(2):105-15. [PubMed:11841783]
- Schultz RM, Dempsey JA: Sequence dependence of Alimta (LY231514, MTA) combined with doxorubicin in ZR-75-1 human breast carcinoma cells. Anticancer Res. 2001 Sep-Oct;21(5):3209-14. [PubMed:11848474]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [PubMed:11252887]
- Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699]
- Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320]
- Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Phosphoribosylglycinamide formyltransferase activity
- Specific Function
- Not Available
- Gene Name
- GART
- Uniprot ID
- P22102
- 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. [PubMed:11848474]
- Hanauske AR, Chen V, Paoletti P, Niyikiza C: Pemetrexed disodium: a novel antifolate clinically active against multiple solid tumors. Oncologist. 2001;6(4):363-73. [PubMed:11524555]
- Molina JR, Adjei AA: The role of Pemetrexed (Alimta , LY231514) in lung cancer therapy. Clin Lung Cancer. 2003 Jul;5(1):21-7. [PubMed:14596699]
- Giovannetti E, Mey V, Nannizzi S, Pasqualetti G, Marini L, Del Tacca M, Danesi R: Cellular and pharmacogenetics foundation of synergistic interaction of pemetrexed and gemcitabine in human non-small-cell lung cancer cells. Mol Pharmacol. 2005 Jul;68(1):110-8. Epub 2005 Mar 28. [PubMed:15795320]
- Kindler HL: Pemetrexed in pancreatic cancer. Semin Oncol. 2002 Dec;29(6 Suppl 18):49-53. [PubMed:12571811]
- Adjei AA: Gemcitabine and Pemetrexed disodium in treating breast cancer. Oncology (Williston Park). 2001 Feb;15(2 Suppl 3):34-7. [PubMed:11252887]
- Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, Lefebvre JL, Gedouin D, Ripoche V, Kayitalire L, Niyikiza C, Johnson R, Latz J, Schneider M: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer. 2001 Sep 1;85(5):649-55. [PubMed:11531245]
- Adjei AA: Gemcitabine and pemetrexed disodium combinations in vitro and in vivo. Lung Cancer. 2001 Dec;34 Suppl 4:S103-5. [PubMed:11742712]
- Adjei AA: Pemetrexed in the treatment of selected solid tumors. Semin Oncol. 2002 Apr;29(2 Suppl 5):50-3. [PubMed:12023793]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Protein homodimerization activity
- Specific Function
- Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). Has broad substrate specificity, and does not display selectivity based...
- 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. [PubMed:21336182]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Nucleoside transmembrane transporter activity
- Specific Function
- Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
- 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. [PubMed:21336182]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
Drug created on June 13, 2005 07:24 / Updated on August 15, 2018 14:26