Alimta® (Pemetrexed)

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Pemetrexed: Mechanism of Action

Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication.

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Detailed Information

The information contained in this letter may not completely match the current local labeling for PEMETREXED. Please see local labeling approved in your country.

Data From In Vitro Studies

Pemetrexed behaves as a multitargeted antifolate by inhibiting several key folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides including

  • TS
  • DHFR, and
  • GARFT.1

Mechanism of Action

  1. Pemetrexed is transported into cells by both the reduced folate carrier and membrane folate binding protein transport systems.1
  2. Once in the cell, pemetrexed is rapidly and efficiently converted to polyglutamate forms by the enzyme folyl polyglutamate synthetase.1
  3. The polyglutamate forms are retained in cells and are even more potent inhibitors of TS and GARFT.1

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

Reference

1Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

DHFR = dihydrofolate reductase

GARFT = glycinamide ribonucleotide formyltransferase

TS = thymidylate synthase 

Fecha de la última revisión: 2020 M07 20


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