Structure activity relationship studies of compounds to treat FD/MAS

MDBRFDMAS
Written By Million Dollar Bike Ride

Awardee: Fernando Fierro

Co-PI: Charles Hoffman

Institution: University of California Davis

Grant Amount: $53,791

Funding Period: February 1, 2022 - January 31, 2023

Summary:

FD lesions contain cells with excess G alpha protein activity that stimulates adenylyl cyclases (ACs), increasing cAMP levels. This disruption of appropriate cell signaling ultimately affects normal bone homeostasis. We propose testing a set of compounds with promising AC-inhibitory activity, with the ultimate goal of developing a therapeutic drug. Our proposal is a collaborative effort among different research groups: Dr. Fierro will identify compounds that reverse GNAS(R201H) or GNAS(R201C) effects in human bone marrow stromal/stem cells. Dr. Hoffman will use yeast to elucidate if the compounds act directly or indirectly on ACs. Dr. Inglese will perform in vitro pharmacokinetic studies with the same compounds.

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Identification and signaling characterization of GNASR201H/C selective inhibitors for FD/MAS
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Unraveling the role of Adiponectin-expressing bone marrow stromal cells in the cellular pathogenesis of Fibrous Dysplasia