Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain

• DOI: 10.1007/s10495-011-0582-4
• Publication Date: 2011-02-21T05:58:29Z
• Authors: Mar Orzáez; Anna Gortat; Mónica Sancho; Rodrigo J. Carbajo; Antonio Pineda-Lu...; Yadira Palacios-R...; Enrique Pérez-Payá
• Keywords: Anti-tumour; 0301 basic medicine; Inhibitor; Binding Sites; Magnetic Resonance Spectroscopy; dequalinium; Caspase 3; screening; Apoptosis; X-Linked Inhibitor of Apoptosis Protein; IAP; Caspase Inhibitors; Protein Structure, Tertiary; 3. Good health; inhibitor; 03 medical and health sciences; XIAP; Dequalinium; Screening; Humans; HeLa Cells; Protein Binding

Inhibitor of apoptosis proteins (IAPs) regulate the activity of caspases in apoptosis. The human X chromosome-encoded IAP (XIAP) is one of the more potent members of the IAP family and it has been described as a central regulator of apoptosis. Thus, molecules that inhibit XIAP could offer therapeutic opportunities to treat unwanted apoptosis inhibition. In the present study we have applied the selective optimization of side activities (SOSA) approach to the discovery of XIAP inhibitors. In this sense, we have identified dequalinium hydrochloride (Dq) as an inhibitor of the XIAP/caspase-3 interaction both in vitro and in cellular assays.