SHY-867 is a pan RAS inhibitor. SHY-867 effectively prevents the binding of K-Ras proteins and other members of the Ras superfamily of small GTPases with EC 50 values of 0.5-3 μM. SHY-867 effectively inhibits the phosphorylation of MEK, ERK1/2, and AKT downstream of K-Ras. SHY-867 inhibits the formation of the Ras-GTP activity complex. SHY-867 can be used to the studies of pancreatic cancer and non-small cell lung cancer [1].
In Vitro, SHY-867 competes with GTP binding to K-Ras WT, the G12D, G12C, and Q61H mutants, as well as Rac-1, Rho-A, Rab5, and Rab35 with IC50s of 2, 2.5, 1.2, 3, 2.5, 3, 0.5 and 0.75 μM[1]. SHY-867 (0.1-1 μM, 72 h) exhibits potent antiproliferative effects in multiple tumor cell lines, including pancreatic cancer (PANC-1, MIA PaCa-2, BxPC3) and non-small cell lung cancer (NCI-H1975, A549, NCI-H1299), with IC50 values ranging from 0.3-1 μM[1]. SHY-867 (0.3-10 μM, 6 h) significantly inhibits the phosphorylation of key signaling molecules induced by EGF in PANC-1, MIA PaCa-2 and NCI-H1975 cells[1]. SHY-867 (1.25-10 μM, 6 h) inhibits Ras-GTP complex formation with an IC50 of 1-3 μM in PANC-1, MIA PaCa-2 and NCI-H1975 cells[1].
References:
[1]. Carta L, et al. Identification of Small-Molecule Inhibitors that Block the GTP-Binding Pocket of K-Ras and Other Members of the Ras Superfamily of Small GTPases. Mol Cancer Ther. 2025 Sep 12:OF1-OF10.
In Vitro, SHY-867 competes with GTP binding to K-Ras WT, the G12D, G12C, and Q61H mutants, as well as Rac-1, Rho-A, Rab5, and Rab35 with IC50s of 2, 2.5, 1.2, 3, 2.5, 3, 0.5 and 0.75 μM[1]. SHY-867 (0.1-1 μM, 72 h) exhibits potent antiproliferative effects in multiple tumor cell lines, including pancreatic cancer (PANC-1, MIA PaCa-2, BxPC3) and non-small cell lung cancer (NCI-H1975, A549, NCI-H1299), with IC50 values ranging from 0.3-1 μM[1]. SHY-867 (0.3-10 μM, 6 h) significantly inhibits the phosphorylation of key signaling molecules induced by EGF in PANC-1, MIA PaCa-2 and NCI-H1975 cells[1]. SHY-867 (1.25-10 μM, 6 h) inhibits Ras-GTP complex formation with an IC50 of 1-3 μM in PANC-1, MIA PaCa-2 and NCI-H1975 cells[1].
References:
[1]. Carta L, et al. Identification of Small-Molecule Inhibitors that Block the GTP-Binding Pocket of K-Ras and Other Members of the Ras Superfamily of Small GTPases. Mol Cancer Ther. 2025 Sep 12:OF1-OF10.