Deciphering the antitumoral activity of quinacrine: Binding to and inhibition of Bcl-xL
Orzáez M, Mondragón L, García-Jareño A, Mosulén S, Pineda-Lucena A, Pérez-Payá E
Bioorganic and Medicinal Chemistry Letters - vol. 19 1592-1595 (2009)
Bioorganic and Medicinal Chemistry Letters
From the screening of a unique collection of 880 off-patent small organic molecules, we have found that quinacrine inhibits the interaction between a BH3 domain-derived peptide and the antiapoptotic protein Bcl-xL. Nuclear magnetic resonance spectroscopy confirmed that quinacrine binds to the hydrophobic groove that Bcl-xL uses for interacting with the BH3 domain of proapoptotic proteins. This activity can contribute to the anticancer activity of quinacrine. © 2009 Elsevier Ltd. All rights reserved.