SHY-855 is a pan-RAS inhibitor that effectively blocks the binding of K-Ras protein and other members of the RAS small GTPase superfamily, with an IC50 value ranging from 0.3 to 5 μM. It efficiently inhibits the phosphorylation of downstream targets such as MEK, ERK1/2, and AKT. Additionally, SHY-855 prevents the formation of Ras-GTP active complexes. This compound can be utilized in research related to pancreatic cancer and non-small cell lung cancer.

KRAS (WT):2.5 μM

SHY-855 competes with GTP to bind to K-Ras WT, G12D, G12C, and Q61H mutants, as well as Rac-1, Rho-A, Rab5, and Rab35, with IC50 values of 2.5, 2.5, 3, 5, 2.5, 2.5, 0.3, and 0.6 μM, respectively. In a range of tumor cell lines, including pancreatic cancer (PANC-1, MIA PaCa-2, BxPC3) and non-small cell lung cancer (NCI-H1975, A549, NCI-H1299), SHY-855 exhibits potent antiproliferative activity with IC50 values between 0.75-2.9 μM. Additionally, SHY-855 (0.3-10 μM, 6 hours) significantly inhibits the phosphorylation of key signaling molecules induced by EGF in PANC-1, MIA PaCa-2, and NCI-H1975 cells. It also inhibits Ras-GTP complex formation in these cells, with IC50 values of 1-3 μM for concentrations between 1.25-10 μM over 6 hours.