A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria.

ABSTRACT: Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy to administer drug combinations with broad-ranging activity against all manifestations of the disease. DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria. We describe studies profiling the biological activity, pharmacological and pharmacokinetic properties, and safety of DSM265, which supported its advancement to human trials. DSM265 is highly selective toward DHODH of the malaria parasite Pla

SUBMITTER: Phillips MA 

PROVIDER: S-EPMC4539048 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature