Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL
A Degterev, A Lugovskoy, M Cardone, B Mulley… - Nature cell …, 2001 - nature.com
Nature cell biology, 2001•nature.com
To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities
of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit
the binding of the Bak BH3 peptide to Bcl-x L. NMR analyses revealed that BH3Is target the
BH3-binding pocket of Bcl-x L. Inhibitors specifically block the BH3-domain-mediated
heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis.
Our results indicate that BH3-dependent heterodimerization is the key function of anti …
of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit
the binding of the Bak BH3 peptide to Bcl-x L. NMR analyses revealed that BH3Is target the
BH3-binding pocket of Bcl-x L. Inhibitors specifically block the BH3-domain-mediated
heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis.
Our results indicate that BH3-dependent heterodimerization is the key function of anti …
Abstract
To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit the binding of the Bak BH3 peptide to Bcl-x L. NMR analyses revealed that BH3Is target the BH3-binding pocket of Bcl-x L. Inhibitors specifically block the BH3-domain-mediated heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis. Our results indicate that BH3-dependent heterodimerization is the key function of anti-apoptotic Bcl-2 family members and is required for the maintenance of cellular homeostasis.
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