Targeted molecules for the treatment of cancerNovel dihdroorotate dehydrogenase (DHODH) small-molecule inhibitors for the treatment of Acute Myeloid Leukemia, Multiple Myeloma, & Graft vs. Host Disease / Leukemia. BackgroundDHODH 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 acute myeloid leukemia (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 in primary AML blasts. AML affects more than 21,000 people annually in the United States. The prevalence of AML in this country is estimated to be over 60,000 people. Hematopoietic stem cell transplantation is still the most successful therapy; however, the five-year survival remains less than 30%. Patients ineligible for stem cell transplant have < 10% cure rate. Technology OverviewRecent research has demonstrated the potential to treat hematologic malignancies through inhibition of dihydroorotate dehydrogenase (DHODH). The Ohio State University, in collaboration with Hendrix College, is developing DHODH inhibitors (DHODHi) for the treatment of hematological malignancies, including acute myeloid leukemia (AML), multiple myeloma (MM), and acute Graft vs. Host Disease (aGVHD). Importantly, OSU is investigating rational therapeutic combination strategies based on its discovery of DHODHi-mediated upregulation of additional druggable targets having clinically approved targeted therapeutics. Stage of Development: Lead optimizationKnown Characteristics of Lead Compound 41:
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Tech IDT2018-003 CollegeLicensing ManagerSchworer, Adam InventorsCategories |