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

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 therapeuti...

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Bibliographic Details
Authors: Orzaez, M, Gortat, A, Sancho, M, Pineda-Lucena, A, Palacios-Rodriguez, Y
Format: article
Status:Published version
Publication Date:2011
Country:España
Institution:Centro de Investigación Principe Felipe (CIPF)
Repository:r-CIPF. Repositorio Institucional Producción Científica del Centro de Investigación Principe Felipe (CIPF)
OAI Identifier:oai:cipf.fundanetsuite.com:p2547
Online Access:https://cipf.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=2547
Access Level:Open access
Keyword:Anti-tumour
Apoptosis
Dequalinium
IAP
Inhibitor
Screening
XIAP
Description
Summary: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.