Reis, Renata A. G.
Calil, Felipe Antunes
Feliciano, Patricia Rosa
Pinheiro, Matheus Pinto
Nonato, M. Cristina
Total Authors: 5
 Georgia State Univ, Dept Chem, Atlanta, GA 30302 - USA
 Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Lab Cristalog Prot, BR-14040903 Ribeirao Preto - Brazil
 MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 - USA
 Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 4
Archives of Biochemistry and Biophysics;
OCT 15 2017.
Web of Science Citations:
The flavoenzyme dihydroorotate dehydrogenase catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate in the fourth of the six conserved enzymatic reactions involved in the de novo pyrimidine biosynthetic pathway. Inhibition of pyrimidine metabolism by selectively targeting DHODHs has been exploited in the development of new therapies against cancer, immunological disorders, bacterial and viral infections, and parasitic diseases. Through a chronological narrative, this review summarizes the efforts of the scientific community to achieve our current understanding of structural and biochemical properties of DHODHs. It also attempts to describe the latest advances in medicinal chemistry for therapeutic development based on the selective inhibition of DHODH, including an overview of the experimental techniques used for ligand screening during the process of drug discovery. (C) 2017 Elsevier Inc. All rights reserved. (AU)