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効能
抗悪性腫瘍薬, 代謝拮抗薬
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化学的特性
Crystalline Solid
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定義
ChEBI: An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 4
1 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).
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一般的な説明
The drug is available in a 100-mg sterile vial for IV use. Thedrug appears to be effective against a range of tumors includingmesothelioma, NSCLC, colorectal cancer, bladdercancer, and lung cancer. The mechanism of action involvesinhibition of TS resulting in inhibition of thymidylate andDNA synthesis. This drug is a pyrrolopyrimidine analog offolate with antifolate activity. Resistance can occur by increasedexpression of TS, decreased binding affinity for TS,or decreased drug transport into cells. The drug is administeredonly via the IV route and distributes to all tissues.Cellular activation to the more potent polyglutamated formsoccurs, and the majority of the dose is excreted unchangedin the urine. The drug interaction and toxicity profiles aresimilar to that of methotrexate.
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作用機序
Like methotrexate, it is actively transported into tumor cells through reduced folate carriers and, in polyglutamated form, inhibits the synthesis of pyrimidine and purine-based nucletotides by disrupting folatedependent metabolic processes . In addition to DHFR, this pyrrolopyrimidine-based inhibitor binds tightly to thymidylate synthase and GAR transformylase.
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臨床応用
Pemetrexed is a novel multitarget antifolate used by the IV route for the treatment of advanced or metastatic nonsmall cell lung cancer and in combination with cisplatin in malignant pleural mesothelioma.
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副作用
Patients on pemetrexed must take folate and vitamin B12 supplements to reduce the risk of bone marrow suppression (neutropenia, thrombocytopenia, and anemia) and GI side effects. Pretreatment with corticosteroids can reduce the risk of drug-induced skin rash. Pemetrexed has a half-life of 3.5 hours and is excreted primarily unchanged via the kidneys. Significant cross-resistance has been noted between pemetrexed and other pyrimidine and folate antagonists.
