LB 42708

Farnesylation, the post-translational addition of a 15-carbon isoprenyl group, alters the function of several proteins, including Ras proteins.^1,2 LB 42708 is a potent inhibitor of farnesyltransferase (FTase), blocking farnesylation of H-Ras, N-Ras, and K-Ras4B with IC₅₀ values of 0.8, 1.2, and 2.0 nM, respectively.³ It displays over 50,000-fold selectivity for FTase over geranylgeranyltransferase I.³ LB 42708 prevents the farnesylation of H-Ras in response to LPS plus IFN-γ (IC₅₀ = 10 nM), preventing activation of NF-κB as well as downstream signaling.³ These effects are obtained both in RAW 264.7 mouse macrophages and in mice.³ LB42708 also inhibits Ras-dependent signaling in endothelial cells, stopping VEGF-mediated angiogenesis both in vitro and in vivo.⁴

WARNING This product is not for human or veterinary use.

1. Appels, N.M.G.M., Beijnen, J.H., and Schellens, J.H.M. Development of farnesyl transferase inhibitors: A review. Oncologist 10(8), 565-578 (2005).

2. Berndt, N., Hamilton, A.D., and Sebti, S.M. Targeting protein prenylation for cancer therapy. Nat. Rev. Cancer 11(11), 775-791 (2011).

3. Na, H.J., Lee, S.J., Kang, Y.C., et al. Inhibition of farnesyltransferase prevents collagen-induced arthritis by down-regulation of inflammatory gene expression through suppression of p21ras-dependent NF-κB activation. J. Immunol. 173(2), 1276-1283 (2004).

4. Kim, C.K., Choi, Y.K., Ha, K.S., et al. The farnesyltransferase inhibitor LB42708 suppresses vascular endothelial growth factor-induced angiogenesis by inhibiting ras-dependent mitogen-activated protein kinase and phosphatidylinositol 3-kinase/Akt signal pathways. Mol. Pharmacol. 78(1), 142-150 (2010).