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Antifolates in clinical development

C H Takimoto1

  • 1Developmental Therapeutics Department, National Cancer Institute, Bethesda Naval Hospital, MD 20889-5105, USA.

Seminars in Oncology
|January 7, 1998
PubMed
Summary
This summary is machine-generated.

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New antifolate drugs in clinical development show distinct properties from methotrexate, offering targeted inhibition of folate-dependent enzymes. Their mechanisms, response rates, and toxicities are under review for potential therapeutic advancements.

Area of Science:

  • Pharmacology
  • Oncology
  • Drug Development

Background:

  • Methotrexate is the established antifolate drug.
  • Novel antifolates possess unique pharmacologic properties, including lipid solubility, cellular transport, and enzyme specificity.
  • These agents target folate-dependent enzymes like dihydrofolate reductase and thymidylate synthase.

Purpose of the Study:

  • To review the current status of novel antifolate compounds in clinical development.
  • To outline their mechanisms of action, clinical response rates, and toxicity profiles.
  • To compare these newer agents with methotrexate.

Main Methods:

  • Review of clinical development status.
  • Analysis of pharmacologic properties (lipid solubility, cellular transport, polyglutamation).

Related Experiment Videos

  • Assessment of enzyme inhibition specificity (dihydrofolate reductase, thymidylate synthase, glycinamide ribonucleotide formyltransferase).

    • Main Results:

    • Several novel antifolates (edatrexate, piritrexim, raltritrexed, LY 231514, AG337, AG331, 1843U89, ZD 9331, lometrexol) are in clinical trials.
    • These compounds exhibit varied mechanisms, differing from methotrexate.
    • Data on clinical response and toxicity are being gathered for these agents.

    Conclusions:

    • Novel antifolates represent a diverse group of agents with distinct pharmacological profiles.
    • Their unique properties may lead to improved efficacy or reduced toxicity compared to methotrexate.
    • Ongoing clinical evaluation is crucial to determine their therapeutic potential.