ZT-12-037-01 is a potent, selective, ATP-competitive STK19 inhibitor with IC50 of 20.04 nM measured as percentage of NRAS phosphorylation.
ZT-12-037-01 shows similar IC50 of 23.96 and 27.94 nM for STK19WTWT STK19D89N respectively.
ZT-12-037-01 displays extremely high kinase selectivity using KINOMEscan against a panel of 468 diverse kinases using an in vitro ATP-site competition binding assay at 1 uM.
ZT-12-037-01 efficiently inhibits phosphorylation of NRAS in a dose- and time-dependent manner, inhibits NRAS activity in a dose-dependent manner but does not affect the levels of H3K9 methylation.
ZT-12-037-01 effectively inhibits NRAS signaling, including the MEK-ERK and PI3K pathways in SK-MEL-2 and WM2032 cells (with NRASQ61R), but the inhibition was much less effective in A375 or UACC62 cells (with NRASWT), effectively inhibits cell growth and induces apoptosis of SK-MEL-2 and WM2032 melanoma cells.