Proguanil hydrochloride (Chloroquanil) is a biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Upon hydrolysis, Proguanil hydrochloride is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.

Pemetrexed disodium (LY-231514) is a parenterally administered folate antagonist and antineoplastic agent, used in the treatment of non-small cell lung cancer and malignant mesothelioma. Pemetrexed disodium therapy has been associated with moderate rates of serum enzyme elevations during therapy, but has not been convincingly linked to instances of acute, clinically apparent liver injury.

WR99210 is a potent, orally available and less toxic dihydrofolate reductase (DHFR) inhibitor (IC50<0.075 nM). WR99210 has good antiparasitic activity against P. vivax and P. falciparum strains (including P. falciparum strains resistant to Pyrimethamine ) and T. gondii.

Methotrexate disodium is an tetrahydrofolate dehydrogenase inhibitor

Trimethoprim (NSC-106568) is a Dihydrofolate Reductase Inhibitor Antibacterial. The mechanism of action of trimethoprim is as a Dihydrofolate Reductase Inhibitor, and Cytochrome P450 2C8 Inhibitor, and Organic Cation Transporter 2 Inhibitor.