title: Characterization of dequalinium as a XIAP antagonist that targets the BIR2 domain.
abstract: 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.
authors.affiliation: Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, Valencia, Spain. morzaez@cipf.es
authors.forename: Mar
authors.initials: M
authors.lastname: Orzáez
authors.forename: Anna
authors.initials: A
authors.lastname: Gortat
authors.forename: Mónica
authors.initials: M
authors.lastname: Sancho
authors.forename: Rodrigo J
authors.initials: RJ
authors.lastname: Carbajo
authors.forename: Antonio
authors.initials: A
authors.lastname: Pineda-Lucena
authors.forename: Yadira
authors.initials: Y
authors.lastname: Palacios-Rodríguez
authors.forename: Enrique
authors.initials: E
authors.lastname: Pérez-Payá
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D003868:Dequalinium / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D061945:Caspase Inhibitors; D051636:X-Linked Inhibitor of Apoptosis Protein; D003868:Dequalinium; D053148:Caspase 3