Small molecule inhibition of NOTCH3 conformational alterations

MDBRCADASIL
Written By Million Dollar Bike Ride

Awardee: Michael Wang

Institution: University of Michigan

Grant Amount: $101,776

Funding Period: February 1, 2025 - January 31, 2026

Summary:

CADASIL is the leading inherited cause of stroke and vascular dementia and is caused by mutations in NOTCH3. Mutations in NOTCH3 result in abnormal conformations of NOTCH3 protein. We reason that drugs that reverse the abnormal conformations of NOTCH3 may be beneficial to patients. This project aims to perform a drug screen to identify chemicals that bind to mutant NOTCH3 and, by doing so, coax it into a more normal conformation. Towards this goal, we have devised a new technique which will help screen through rationally selected drug candidates. If successful, this would be a first step in drug discovery for CADASIL, currently an untreatable disease.

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