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Antifolate inhibitors of thymidylate synthase as anticancer drugs

A Jarmuła1

  • 1Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warszawa, Poland. a.jarmula@nencki.gov.pl

Mini Reviews in Medicinal Chemistry
|September 22, 2010
PubMed

Insights

Anticancer drugs targeting thymidylate synthase (TS) are crucial for tumor treatment. This review details current antifolate TS inhibitors, their clinical development, and strategies to overcome drug resistance for improved cancer therapy.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Thymidylate synthase (TS) inhibitors are vital in cancer chemotherapy.
  • Several antifolate TS inhibitors are approved or in clinical development.

Purpose of the Study:

  • To review the biochemical and pharmacological properties of antifolate TS inhibitors.
  • To present updated clinical development status of these agents.
  • To discuss future perspectives and drug resistance mechanisms.

Main Methods:

  • Literature review of antifolate TS inhibitors.
  • Analysis of clinical trial data and pharmacological properties.
  • Discussion of drug resistance mechanisms and overcoming strategies.

Main Results:

  • Raltitrexed and Pemetrexed are licensed anticancer drugs, with Pemetrexed in further development.
  • Plevitrexed, GW7904L, Nolatrexed, and BGC 945 show promising anticancer activities.
  • Drug resistance remains a significant challenge in antifolate therapy.

Conclusions:

  • Antifolate TS inhibitors represent a key therapeutic strategy for various cancers.
  • Ongoing research focuses on developing improved agents and overcoming resistance.
  • Understanding resistance mechanisms is crucial for advancing antifolate-based cancer treatment.

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