Suggestions derived from a previous ligand-based ligand design approach and docking calcns. aimed at finding compd. with affinity toward Abl and mol. scaffolds previously untested as Abl inhibitors, led to the identification of com. available N-(thiazol-2-yl)-2-thiophene carboxamide derivs. with affinity in a cell-free assay up to low nanomolar concns., significantly enhanced with respect to that of their parent compds. previously reported. In particular, among compds. of the Asinex database, mol. docking simulations guided the choice of high-affinity ligands, predicting their binding mode and their interaction pattern with the Abl catalytic binding site. Moreover, affinity of the new compds. was also rationalized in terms of their interactions with the enzyme.

N-(thiazol-2-yl)-2-thiophene carboxamide derivatives as Abl inhibitors identified by a pharmacophore-based database screening of commercially available compounds.

SCHENONE, SILVIA;
2008

Abstract

Suggestions derived from a previous ligand-based ligand design approach and docking calcns. aimed at finding compd. with affinity toward Abl and mol. scaffolds previously untested as Abl inhibitors, led to the identification of com. available N-(thiazol-2-yl)-2-thiophene carboxamide derivs. with affinity in a cell-free assay up to low nanomolar concns., significantly enhanced with respect to that of their parent compds. previously reported. In particular, among compds. of the Asinex database, mol. docking simulations guided the choice of high-affinity ligands, predicting their binding mode and their interaction pattern with the Abl catalytic binding site. Moreover, affinity of the new compds. was also rationalized in terms of their interactions with the enzyme.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/223323
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