KRAS-Q61X inhibitor compound 2 is a specific small molecule ligand of KRAS-Q61X (X = H, L, K, R), selectively activates GTP hydrolysis of KRAS-Q61X, suppresses KRAS-Q61X signaling.
KRAS-Q61X inhibitor compound 2 (0-100 uM) exhibited concentration-dependent and time-dependent reduction of RAS·GTP levels on Rasless MEFs expressing KRAS-Q61R, showed suppression of ERK phosphorylation (T202/Y204) with IC50 of 10 uM (4 h).
KRAS-Q61X inhibitor compound 2 (30 uM) reduced RAS·GTP and p-ERK levels in KRAS-Q61L Rasless MEF cells and human embryonic kidney 293 cells expressing SV40 large T anti gen (HEK-293T) transfected with full-length KRASQ61K, KRASQ61H and KRASQ61R alleles.
KRAS-Q61X inhibitor compound 2 (30 uM) demonstrated reduction of RAS·GTP and p-ERK levels in KRAS mutant cell lines, but not A375 (KRASWT).
KRAS-Q61X inhibitor compound 2 is active in cells and functions as a KRAS-Q61X accelerator by promot ing GTP hydrolysis, thereby suppressing downstream ERK signaling in a RAS-dependent manner.