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DHODH Inhibitors for Treatment of Hematological Malignancies
The Ohio State University
Small molecule
Hematology
Hit To Lead or Lead Optimization
DHODH is a rate-limiting enzyme in de novo pyrimidine synthesis. Rapidly dividing cancer cells are therefore sensitive to blockade of this pathway. New research has shown DHODH inhibition can induce differentiation in AML cell lines, translating to increased survival in animal models. There is also evidence that DHODH inhibitors can produce cytotoxic effects through p53 upregulation and mitochondrial effects.