Debromohymenialdisine

Debromohymenialdisine (DBH) is a marine sponge alkaloid that inhibits Chk1 and Chk2 (IC₅₀ = 3 and 3.5 µM, respectively), blocking G₂ arrest.^1,2 Because it does not significantly affect the activity of ataxia-telangiectasia mutated (ATM) or ATM-Tad2-related protein, DBH is a useful tool for studying the roles of Chk1 and Chk2 in DNA repair and cell cycle regulation.¹ DBH also inhibits MAP kinase kinase 1 (IC₅₀ = 881 nM), glycogen synthase kinase 3β (IC₅₀ = 1.39 μM), cyclin-dependent kinase 5/p25 (IC₅₀ = 9.12 μM), protein tyrosine kinase 6 (IC₅₀ = 0.6 μM), and other kinases largely unrelated to DNA damage/repair and cell cycling.^3,4,5,6

WARNING This product is not for human or veterinary use.

1. Curman, D., Cinel, B., Williams, D.E., et al. Inhibition of the G₂ DNA damage checkpoint and of protein kinases Chk1 and Chk2 by the marine sponge alkaloid debromohymenialdisine. The Journal of Biological Chemisty 276(21), 17914-17919 (2001).

2. Saleem, R.S.Z., Lansdell, T.A., and Tepe, J.J. Synthesis and evaluation of debromohymenialdisine-derived Chk2 inhibitors. Bioorg. Med. Chem. 20(4), 1475-1481 (2012).

3. Tasdemir, D., Mallon, R., Greenstein, M., et al. Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J. Med. Chem. 45(2), 529-532 (2002).

4. Wan, Y., Hur, W., Cho, C.Y., et al. Synthesis and target identification of hymenialdisine analogs. Chem. Biol. 11(2), 247-259 (2004).

5. Jobson, A.G., Cardellina, J.H., II, Scudiero, D., et al. Identification of a bis-guanylhydrazone [4,4'-diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase. Mol. Pharm. 72(4), 876-884 (2007).

6. Foloppe, N., Fisher, L.M., Francis, G., et al. Identification of a buried pocket for potent and selective inhibition of Chk1: Prediction and verification. Bioorg. Med. Chem. 14(6), 1792-1804 (2006).