LB42708 (LB-42708) is a potent, selective and orally active farnesyltransferase (FTase) inhibitor, inhibits farnesylation of H-Ras, N-Ras and K-Ras4B with IC50 values of 0.8 nM, 1.2 nM and 2.0 nM, respectively, inhibits p21(ras)-dependent NF-kappaB activation.
LB42708 suppressed NF-kappaB activation and iNOS promoter activity by suppressing the I-kappaB kinase activity and I-kappaBalpha degradation.
LB42708 significantly decreased the incidence and severity of arthritis as well as mRNA expression of inducible NO synthase, cyclooxygenase-2, TNF-alpha, and IL-1beta in the paws of collagen-induced arthritic mice.
LB42708 inhibited VEGF-induced Ras activation and subsequently suppressed angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase/p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric-oxide synthase pathways in endothelial cells without altering FAK/Src activation.
LB42708 suppressed tumor growth and tumor angiogenesis in both xenograft tumor models of Ras-mutated HCT116 cells and its wild-type Caco-2 cells.