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., 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.
|Data di pubblicazione:||2012|
|Titolo:||Receptor-guided 3D-QSAR approach for the discovery of c-kit tyrosine kinase inhibitors|
|Citazione:||Almerico, A., 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.|
|Digital Object Identifier (DOI):||http://dx.doi.org/DOI 10.1007/s00894-011-1304-0|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Appare nelle tipologie:||1.01 Articolo in rivista|