The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies.
Human dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the rate-limiting step in de novo pyrimidine biosynthesis, is considered to be an attractive target for potential treatment of autoimmune disease and cancer.
However, human DHODH inhibitors have also been investigated as treatment for cancer, parasite infections (i.e. malaria) and viruses as well as in the agrochemicals industry.
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.
Inhibitors of human DHODH have been used to treat autoimmune diseases such as, rheumatoid arthritis or multiple sclerosis and have been investigated in the treatment of cancer, viral diseases, as well as in plant pathology.
The correlations between DHODH protein expression, proliferation speed and sensitivity to DHODH inhibitors were also investigated in a panel of cancer cell lines.