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- 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- 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- , 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.

Lauria, A., Ippolito, M., Fazzari, M., Tutone, M., Di Blasi, F., Mingoia, F., et al. (2010). IKK-beta inhibitors: An analysis of drug–receptor interaction by using Molecular Docking and Pharmacophore 3D-QSAR approaches. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 29(1), 72-81 [10.1016/j.jmgm.2010.04.008].

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

LAURIA, Antonino;FAZZARI, Marco;TUTONE, Marco;ALMERICO, Anna Maria
2010-01-01

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- 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- 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- , 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.
Settore CHIM/08 - Chimica Farmaceutica
Lauria, A., Ippolito, M., Fazzari, M., Tutone, M., Di Blasi, F., Mingoia, F., et al. (2010). IKK-beta inhibitors: An analysis of drug–receptor interaction by using Molecular Docking and Pharmacophore 3D-QSAR approaches. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 29(1), 72-81 [10.1016/j.jmgm.2010.04.008].
File in questo prodotto:
File Dimensione Formato  
JMGM_2010.pdf

Solo gestori archvio

Dimensione 1.07 MB
Formato Adobe PDF
1.07 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/51314
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 40
  • ???jsp.display-item.citation.isi??? 36
social impact