First molecules to reactivate RAS^G12V GTPase activity.

ABSTRACT:

Background

Small-molecule compounds that even partially restore the GTPase activity of RAS^G12V can be used in anticancer therapy. Until now, attempts to obtain such compounds have failed. Compounds with this ability have been defined in our research.

Methods

The compounds were initially identified through virtual screening, and their optimal binding conformation in the RAS SW-II pocket was determined using the flexible docking technique. Efficacy was verified based on the IC50 determination, GTPase activity, as well as the AKT and ERK phospho WB assays.

Results

The IC50 of the tested compounds was significantly lower against cells with the RAS^G12V mutation than against selected types of normal cells. The molecular mechanism of action of these com

SUBMITTER: Wlodarczyk A 

PROVIDER: S-EPMC11783748 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature