GNF-5

GNF-5 is an allosteric inhibitor of Bcr-Abl (IC₅₀ = 0.121 µM) and a derivative of GNF-2 (Item No. 16253).¹ It also inhibits the Bcr-Abl mutants Bcr-Abl^G250E, Bcr-Abl^E255V, and Bcr-Abl^M351T (IC₅₀s = 4.52, 0.38, and 0.93 µM, respectively).² GNF-5 inhibits the growth of Ba/F3 cells (IC₅₀ = 0.145 µM).¹ It reduces viral titers in Vero cells infected with infectious bronchitis virus (IBV), a coronavirus, when used at a concentration of 10 µM via inhibition of IBV surface glycoprotein-induced syncytia formation and virus-cell fusion.³ GNF-5 (75 mg/kg) increases survival in a recalcitrant mutant Bcr-Abl^T315I mouse bone marrow transplantation model when administered alone or in combination with nilotinib.²

WARNING This product is not for human or veterinary use.

1. Fabbro, D., Manley, P.W., Jahnke, W., et al. Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site. Biochim. Biophys. Acta 1804(3), 454-462 (2010).

2. Zhang, J., Adrián, F.J., Jahnke, W., et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature 463(7280), 501-506 (2010).

3. Sisk, J.M., Frieman, M.B., and Machamer, C.E. Coronavirus S protein-induced fusion is blocked prior to hemifusion by Able kinase inhibitors. J. Gen. Virol. 99(5), 619-630 (2018).