Develop Small Molecule Regulators of GTPase-activating Proteins of ADP-ribosylation Factors (ARFGAPs)

Develop Small Molecule Regulators of GTPase-activating Proteins of ADP-ribosylation Factors (ARFGAPs) Public Deposited

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Sun, Wei
- Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry

Abstract

GTPase-activating proteins of ADP-ribosylation factors (ARFGAPs) play essential roles in cell growth and migration, tumor invasion and neuronal development. Increasing evidence also implicates that ARFGAPs are involved in cancer, Alzheimer's disease, and autism. However, the precise mechanisms whereby ARFGAPs regulate different diseases are yet to be elucidated. Consequently, direct and efficient regulators of ARFGAPs are urgently needed. In this thesis, I describe our efforts in developing small molecule ARFGAP inhibitors. It has been reported that a small molecule, QS11, potentially inhibits multiple ARFGAPs and is able to activate the Wnt/β-catenin signaling pathway. However, the mechanism of how QS11 inhibits different ARFGAPs is not well known. To define the molecular basis of the regulation of ARFGAP1 by QS11, we demonst

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