DSM 265 is an antimalarial agent and inhibitor of P. falciparum and P. vivax dihydroorotate dehydrogenase (DHODH; IC50s = 8.9 and 27 nM, respectively).1 It is selective for P. falciparum and P. vivax DHODH over human, rabbit, pig, and monkey DHODH (IC50s = >41 ?g/ml) but does inhibit P. cynomolgi, dog, mouse, and rat DHODH (IC50s = 0.005, 11, 1.1, and 0.82 ?g/ml, respectively).2 DSM 265 inhibits the growth of the P. falciparum strain 3D7 with an EC50 value of 4.3 nM.1 It also reduces blood parasitemia in mice (ED90 = 1.5 mg/kg twice per day).2
1.Kokkonda, S., Deng, X., White, K.L., et al.Tetrahydro-2-naphthyl and 2-indanyl triazolopyrimidines targeting Plasmodium falciparum dihydroorotate dehydrogenase display potent and selective antimalarial activityJ. Med. Chem.59(11)5416-5431(2016) 2.Phillips, M.A., Lotharius, J., Marsh, K., et al.A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malariaSci. Transl. Med.7(296)296ra111(2015)