In vitro activity: LB42708 potently inhibits the processing of the cellular farnesylated protein p21ras induced by LPS + IFN-γ in murine macrophage cell line RAW264.7 cells. LB42708 inhibits NF-κB activation and iNOS promoter activity through the inhibition of IKK activity. Moreover, LB42708 suppresses the expression of inducible NO synthase, cyclooxygenase-2, TNF-alpha, and IL-1beta and the production of NO and PGE(2) in immune-activated macrophages and osteoblasts. LB42708 irreversibly inhibits growth and induces apoptosis in H-ras and K-ras-transformed rat intestinal epithelial cells. LB42708 inhibits of VEGF-induced tumor angiogenesis by blocking Ras-dependent MAPK and PI3K/Akt pathways in tumor-associated endothelial cells.

Cell Assay: Cell growth is measured by MTT. Briefly, cells were seeded at 2 × 103 cells per well in 96-well culture plates in triplicate. After the addition of various concentrations of drugs, cells are incubated for 72 h. At the end of culture, the plates are washed twice with PBS, and cells are incubated with 200 μl of RPMI 1640 containing 10% FCS and 0.25 mg/ml of MTT at 37 °C for 3 h. The absorbance of each well is measured with Titer-Tech 96-well multiscanner at 570 nm. The viable cell number is proportional to the absorbance.

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