Survivin is a cellular protein implicated in cell survival by interacting with and inhibiting the apoptotic function of several proteins including Smac/DIABLO, caspase-
3, and caspase-
7.
1,2 Survivin also plays a role in the regulation of the cell cycle as part of a protein complex that includes INCENP, Aurora B kinase, and Borealin. CAY10625 is an antagonist of the interaction between survivin and the apoptosis-
promoting protein Smac/DIABLO, exhibiting an IC
50 value of 2.2 μM.
3 It inhibits the interaction of survivin with INCENP less effectively with an IC
50 value of 20 μM. CAY10625 is cell-
permeable and sensitizes cells to the induction of apoptosis by doxorubicin.
3
1. Ryan, B.M., O'Donovan, N., and Duffy, M.J. Survivin: A new target for anti-cancer therapy Cancer Treat. Rev. 35,553-562(2009).
2. Shin, S., Sung, B.J., Cho, Y.S., et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7 Biochemistry 40,1117-1123(2001).
3. Oikawa, T., Unno, Y., Matsuno, K., et al. Identification of a small-molecule inhibitor of the interaction between Survivin and Smac/DIABLO Biochem. Biophys. Res. Commun. 393,253-258(2010).
