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Folate and antifolate pharmacology

B Kamen1

  • 1Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas 75235-9063, USA.

Seminars in Oncology
|January 7, 1998
PubMed
Summary

Folic acid (folate) is vital for cell growth and replication. Folate analogues are used as drugs for cancer and infections, with new analogues showing unique properties and clinical applications.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Molecular Biology

Background:

  • Folate is an essential B vitamin crucial for one-carbon metabolism, DNA synthesis, and cell replication.
  • Folate analogues are established therapeutics for cancer, autoimmune diseases, and infections.
  • Extensive research has elucidated folate homeostasis pathways and enzyme structures.

Purpose of the Study:

  • To review folate homeostasis and metabolism.
  • To compare natural folate with antifolates.
  • To present the pharmacology of methotrexate and next-generation antifolates.

Main Methods:

  • Review of existing literature on folate biochemistry and pharmacology.
  • Analysis of enzyme structures and gene sequencing data.
  • Pharmacological profiling of antifolate drugs.

Main Results:

  • Folate's role as a one-carbon donor is critical for purine and thymidine synthesis.
  • Folate analogues exhibit diverse transport, metabolism, and target interactions.
  • Next-generation antifolates like trimetrexate and raltritrexed offer unique biochemical profiles.

Conclusions:

  • Folate analogues are versatile therapeutic agents.
  • Understanding folate metabolism is key to developing novel antifolates.
  • Ongoing research focuses on new antifolates and mechanisms of drug resistance.

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