pfdhfr

WR99210 hydrochloride is a potent inhibitor of Plasmodium falciparum dihydrofolate reductase (pfDHFR), which is a major malarial drug target. It has subnanomolar potency for the wild type, double mutant and quadruple mutant dihydrofolate reductases.

DHFR-IN-20 (Compound LA1) is an inhibitor of dihydrofolate reductase (DHFR) targeting the malignant strains of the malaria parasite. It exhibits inhibition constants (Kis) of 0.16 nM, 0.30 nM, and 6.6 nM for PfDHFR-WT, PfDHFR-QM, and HsDHFR, respectively. Additionally, DHFR-IN-20 demonstrates antimalarial activity, with IC50 values of 1.4 nM against parasites carrying the wild-type (TM4 8.2) PfDHFR enzyme and 1.6 μM against those with the quadruple mutation (V1 S)PfDHFR.