Studies of the the three-dimensional quantitative structure–activity relationships for ninety-five c-kit tyrosine kinase inhibitors were performed. Based on a cocrystallized compound (1 T46), known inhibitors were aligned with c-kit by induced-fit docking, and multiple training/test set splitting was performed to validate the selected pharmacophore model. The best pharmacophore model consisted of five features: one hydrogen-bond donor and four aromatic rings. Reliable statistics were obtained (R2=0.95, Rpred 2=0.75), and the model was validated by using it to select c-kit inhibitors from a database; 82.1% of the hits it retrieved were active. Accordingly, our model can be reliably used to identify new c-kit inhibitors, and can provide useful information when designing new inhibitors.

ALMERICO, A.M., TUTONE, M., & LAURIA, A. (2012). Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors. JOURNAL OF MOLECULAR MODELING, 18, 2885-2895 [DOI 10.1007/s00894-011-1304-0].

Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors

ALMERICO, Anna Maria;TUTONE, Marco;LAURIA, Antonino
2012

Abstract

Studies of the the three-dimensional quantitative structure–activity relationships for ninety-five c-kit tyrosine kinase inhibitors were performed. Based on a cocrystallized compound (1 T46), known inhibitors were aligned with c-kit by induced-fit docking, and multiple training/test set splitting was performed to validate the selected pharmacophore model. The best pharmacophore model consisted of five features: one hydrogen-bond donor and four aromatic rings. Reliable statistics were obtained (R2=0.95, Rpred 2=0.75), and the model was validated by using it to select c-kit inhibitors from a database; 82.1% of the hits it retrieved were active. Accordingly, our model can be reliably used to identify new c-kit inhibitors, and can provide useful information when designing new inhibitors.
Settore CHIM/08 - Chimica Farmaceutica
ALMERICO, A.M., TUTONE, M., & LAURIA, A. (2012). Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors. JOURNAL OF MOLECULAR MODELING, 18, 2885-2895 [DOI 10.1007/s00894-011-1304-0].
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10447/64271
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