New antifolates in clinical development.

C H Takimoto; C J Allegra

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PubMed · 8924375

New antifolates in clinical development.

C H Takimoto·C J Allegra

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Abstract

Numerous new antifolate drugs have been developed in an attempt to overcome the potential mechanisms of tumor cell resistance to methotrexate, which can include decreased drug transport into cells; decreased polyglutamation, leading to increased drug efflux from cells; decreased drug affinity for folate-dependent enzymes; mutations of dihydrofolate reductase (DHFR), a key enzyme required for the maintenance of adequate intracellular reduced folate levels that is inhibited by methotrexate; and increased expression of the DHFR protein. Promising antifolate compounds undergoing clinical testing as anticancer agents include trimetrexate (which was recently approved by the FDA for the treatment of Pneumocystis carinii pneumonia), edatrexate, piritrexim, Tomudex, and lometrexol. The mechanisms of action, dosage, pharmacokinetics, clinical toxicity, and antitumor activity of these drugs are profiled.

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Aminopterin Antimetabolites, Antineoplastic Antineoplastic Agents Drugs, Investigational Folic Acid Antagonists Humans Neoplasms Pyrimidines Quinazolines Thiophenes Trimetrexate Journal Article Review

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C H Takimoto, C J Allegra. 1995. New antifolates in clinical development.. https://pubmed.ncbi.nlm.nih.gov/8924375/

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