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|Title:||Identification of the First Non-Peptidic Small Molecule Inhibitor of the c-Abl/14-3-3 Protein-Protein Interactions Able to Drive Sensitive and Imatinib-Resistant Leukemia Cells to Apoptosis||Authors:||Corradi, V
SANTUCCI M., A
|Keywords:||14-3-3 Proteins; Drug discovery; Leukemia; Molecular modeling; Non-peptidic compounds; Protein-protein interactions||Issue Date:||2010||Project:||None||Journal:||BIOORGANIC & MEDICINAL CHEMISTRY LETTERS||Abstract:||
An in silico structure-based ligand design approach resulted in the identification of the first non-peptidic small molecule able to inhibit protein-protein interactions between 14-3-3 and c-Abl. This compound shows an anti-proliferative effect on human leukemia cells either sensitive or resistant to Imatinib, in consequence of the T315I mutation. It also mediates c-Abl release from 14-3-3 in a way similar to that found in response to Imatinib treatment.
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