6533b830fe1ef96bd129704f

RESEARCH PRODUCT

IKK-β inhibitors: An analysis of drug–receptor interaction by using Molecular Docking and Pharmacophore 3D-QSAR approaches

Mario IppolitoAntonino LauriaFrancesco MingoiaMarco TutoneMarco FazzariFrancesco Di BlasiAnna Maria Almerico

subject

Models MolecularQuantitative structure–activity relationshipReceptors DrugMolecular Sequence DataQuantitative Structure-Activity RelationshipIκB kinaseComputational biologyPharmacologyBiologyMaterials ChemistryHumansAmino Acid SequenceNF-kBHomology modelingPhysical and Theoretical ChemistryProtein Kinase InhibitorsTranscription factorSpectroscopyIKK-betaIKK-beta inhibitors Molecular Docking Pharmacophore 3D-QSAR approachesBinding SitesPharmacophoreKinaseHomology modelingSettore CHIM/08 - Chimica FarmaceuticaComputer Graphics and Computer-Aided DesignI-kappa B KinaseMolecular DockingStructural Homology ProteinBiological targetDrug receptorPharmacophore

description

Abstract The IKK kinases family represents a thrilling area of research because of its importance in regulating the activity of NF-kB transcription factors. The discovery of the central role played by IKK-β in the activation of transcription in response to apoptotic or inflammatory stimuli allowed to considerate its modulation as a promising tool for the treatment of chronic inflammation and cancer. To date, several IKK-β inhibitors have been discovered and tested. In this work, an analysis of the interactions between different classes of inhibitors and their biological target was performed, through the application of Molecular Docking and Pharmacophore/3D-QSAR approaches to a set of 141 inhibitors included in the Binding Database. In order to overcome the difficulty due to the lack of crystallographic data for IKK-β, a homology model of this protein has been built and validated. The results allowed to study in depth the structural bases for the interaction of each family of inhibitors and provided clues for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting this enzyme.

yearjournalcountryeditionlanguage
2010-01-01Journal of Molecular Graphics and Modelling
https://doi.org/10.1016/j.jmgm.2010.04.008