Structural insights into IKKbeta inhibition by natural products staurosporine and quercetin.
This Letter describes the results of two combined approaches: homology modeling and molecular docking studies, in order to propose the molecular basis of IKKbeta inhibition by staurosporine and quercetin as ATP-competitive inhibitors. The results provides a rationale and structural frameworks for designing potent ATP binding-site inhibitors of IKKbeta, which is an attractive drug target for inflammatory diseases and has been found to be responsible for some of the already observed pharmacological effects for marketed drugs.
Avila
Carolina M
CM
LASSBio-Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil.
Romeiro
Nelilma C
NC
Sant'Anna
Carlos M R
CM
Barreiro
Eliezer J
EJ
Fraga
Carlos A M
CA
D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D011794:Quercetin / Q000737:chemistry* / Q000494:pharmacology; D019311:Staurosporine / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001688:Biological Products; D011794:Quercetin; D051550:I-kappa B Kinase; D019311:Staurosporine