DHODH-IN-8

DHODH-IN-8 (Compound 27) is an inhibitor of human and Plasmodium falciparum dihydroorotate dehydrogenase (DHODH) with IC50s of 0.13 μM and 47.4 μM, and Kis of 0.016 μM and 5.6 μM, respectively. DHODH-IN-8 has antimalarial activity[1].

Research Areas >> Infection

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Signaling Pathways >> Metabolic Enzyme/Protease >> Lactate Dehydrogenase

IC50: 0.13 μM (human DHODH) and 47.4 μM (Plasmodium falciparum DHODH)[1] Ki: 0.016 μM (human DHODH) and 5.6 μM (Plasmodium falciparum DHODH)[1]

The dihydroorotate dehydrogenases (DHODHs) are attractive chemotherapeutic targets in various pathogens, such as Plasmodium falciparum and Helicobacter pylori, and for the treatment of human disease. DHODH catalyzes the conversion of dihydroorotate (DHO) to orotate by utilizing an FMN cofactor in the only redox reaction present in the pyrimidine biosynthesis pathway. The human DHODH (HsDHODH)a and the P. falciparum DHODH (PfDHODH) both belong to the group of class 2 DHODHs that use respiratory quinones as the terminal electron acceptors[1].

[1]. Davies M, et al. Structure-based design, synthesis, and characterization of inhibitors of human and Plasmodium falciparum dihydroorotate dehydrogenases. J Med Chem. 2009 May 14;52(9):2683-93.