Supporting data for "Covalent inhibitor for targeting RhoA in CRC treatment"

Abstract of thesis entitledCovalent inhibitor targeting RhoA GTPase in CRC treatmentSubmitted byJason Ying Ki LIfor the degree of Master of Philosophyat The University of Hong Kong in August 2023RhoA GTPase is associated with tumor progression in many cancers. Elevated RhoA activity was reported in colorectal cancer (CRC). RhoA in cancer mainly regulates cell motility and mechanotransduction through the Rho/ROCK pathway that eventually leads to cancer migration, invasion, proliferation and survival. RhoA also regulates other cancer related pathways such as remodulating tumor microenvironment (TME) by governing actin contractility in microvesicle formation. All these suggested RhoA harboring immense therapeutic benefits and hence is a good target for cancertreatment. However, progress of drug discovery on RhoA was slow due to the fact that the protein lacks a deep binding pocket for small molecule compounds, as well as its nanomolar range affinity towards its nucleotide substrate that makes the development of substrate analogs as competitors difficult. Hence RhoA was regarded as undruggable by conventional drug screen strategies.In this project, we demonstrated the use of a chemoproteomics platform to discover a potent and specific RhoA inhibitor 1F2 in treatment of CRC.f8dsaf8dsa