Pemetrexed

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Pemetrexed
Systematic (IUPAC) name
2-[4-[2-(4-amino-2-oxo-3,5,7-triazabicyclo[4.3.0] nona-3,8,10-trien-9-yl)ethyl] benzoyl] aminopentanedioic acid
Identifiers
CAS number	137281-23-3
ATC code	L01BA04
PubChem	60843
DrugBank	APRD00573
Chemical data
Formula	C₂₀H₂₁N₅O₆
Mol. mass	427.411 g/mol
Pharmacokinetic data
Bioavailability	NA
Protein binding	81%
Metabolism	Negligible
Half life	3.5 hours
Excretion	Renal
Therapeutic considerations
Licence data	EU US
Pregnancy cat.	D(US)
Legal status	POM(UK) ℞-only(US)
Routes	IV

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.

1 History
2 Mechanism of action
3 Clinical use
4 External links

[edit] History

The molecular structure of pemetrexed was developed by Edward C. Taylor at Princeton University and clinically developed by Indianapolis based drug maker, Eli Lilly and Company.

[edit] Mechanism of action

Pemetrexed is chemically similar to folic acid and is in the class of chemotherapy drugs called folate antimetabolites. It works by inhibiting three enzymes used in purine and pyrimidine synthesis—thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT). By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cells.

[edit] Clinical use

In February 2004, the Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma, a type of tumor of the lining of the lung, in combination with cisplatin. In July 2004, the FDA granted approval as a second-line agent for the treatment of non-small cell lung cancer. Trials are currently testing it against esophagus and other cancers.

Patients are required to be on folic acid and vitamin B12 supplementation when they are on pemetrexed therapy. (In clinical trials for mesothelioma, folic acid and B12 supplementation reduced the frequency of adverse events.) It is also recommended for patients to be on a steroid (e.g. dexamethasone 4mg twice daily) on the day prior, day of, and day after pemetrexed infusion to avoid skin rashes.

[edit] External links

Alimta website
Alimta / Pemetrexed Virtual Cancer Centre
NCI Drug Information Summary on Pemetrexed Disodium

v • d • e Chemotherapeutic agents/Antineoplastic agents (L01)
Alkylating agents	Nitrogen mustards: (Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan). Nitrosoureas:(Carmustine, Fotemustine, Lomustine, Streptozocin). Platinum: (Carboplatin, Cisplatin, Oxaliplatin, BBR3464). Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, Uramustine
Antimetabolites	Folic acid: (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed). Purine:(Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine). Pyrimidine:(Capecitabine, Cytarabine, Fluorouracil, Floxuridine, Gemcitabine)
Spindle poison plant alkaloids	Taxane: (Docetaxel, Paclitaxel). Vinca: (Vinblastine, Vincristine, Vindesine, Vinorelbine).
Cytotoxic/antitumor antibiotics	Anthracycline family: (Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitoxantrone, Valrubicin). Bleomycin, Hydroxyurea, Mitomycin, Actinomycin
Topoisomerase inhibitors	Camptotheca: (Camptothecin, Topotecan, Irinotecan), Podophyllum:(Etoposide, Teniposide).
CI monoclonal antibodies	Alemtuzumab, Bevacizumab, Cetuximab, Gemtuzumab, Panitumumab, Rituximab, Tositumomab, Trastuzumab
Photosensitizers	Aminolevulinic acid, Methyl aminolevulinate, Porfimer sodium, Verteporfin
Kinase inhibitors	Dasatinib, Erlotinib, Gefitinib, Imatinib, Lapatinib, Nilotinib, Sorafenib, Sunitinib, Vandetanib (ZD6474)
Other	Alitretinoin, Altretamine, Amsacrine, Anagrelide, Arsenic trioxide, Asparaginase, Bexarotene, Bortezomib, Denileukin diftitox, Estramustine, Hydroxycarbamide, Masoprocol, Mitotane, Pegaspargase, Tretinoin