The dihydroorotate dehydrogenases: Past and present

Area of Science:

• Biochemistry
• Enzymology
• Medicinal Chemistry

Background:

• Dihydroorotate dehydrogenase (DHODH) is a key enzyme in the de novo pyrimidine biosynthesis pathway.
• DHODH catalyzes the stereoselective oxidation of (S)-dihydroorotate to orotate.
• Inhibition of DHODH is a validated strategy for treating cancer, immunological disorders, and infectious diseases.

Purpose of the Study:

• To provide a chronological overview of the scientific understanding of DHODH.
• To summarize recent advances in medicinal chemistry for DHODH-targeted drug development.
• To present an overview of ligand screening techniques in DHODH inhibitor discovery.

Main Methods:

• Literature review of structural and biochemical studies on DHODHs.
• Analysis of medicinal chemistry efforts in developing DHODH inhibitors.
• Overview of experimental techniques for ligand screening.

Main Results:

• Comprehensive summary of DHODH structural and biochemical properties.
• Detailed account of therapeutic development strategies targeting DHODH.
• Inclusion of experimental methodologies for drug discovery.

Conclusions:

• DHODH remains a significant target for therapeutic intervention.
• Advances in understanding DHODH structure and function facilitate drug design.
• Continued research in medicinal chemistry and screening techniques will drive the development of novel DHODH inhibitors.