tcsc2281 GDC-0623

GDC-0623 (RG 7421) is a potent, ATP-uncompetitive inhibitor of MEK1 (K_i=0.13 nM, +ATP), and displays 6-fold weaker potency against HCT116 (KRAS (G13D), EC₅₀=42 nM) versus A375 (BRAF^V600E, EC₅₀=7 nM).

IC50 & Target: Ki: 0.13 nM (MEK1,+ATP)

In Vitro: GDC-0623 (RG 7421) and G-573 are able to prevent MEK phosphorylation by CRAF in vitro, and able to block MEK phosphorylation by BRAF(V600E)^[1]. GDC-0623 (RG 7421) is potent, ATP-uncompetitive inhibitors of MEK1 but shows distinct shifts in cellular activity compared with the other two inhibitors, only 6-fold half-maximum effective concentration (EC₅₀) decreases^[2].

In Vivo: GDC-0623 (RG 7421) (40 mg/kg, p.o.) shows percent tumour growth inhibition (%TGI) in MiaPaCa-2 xenograft model. GDC-0623 (RG 7421) and G-573 show superior antitumour activity compared to GDC-0623 (RG 7421) in all three KRAS models^[1].