title: Combination of pharmacophore model development and binding mode analyses: identification of ligand features essential for IκB kinase-beta (IKKβ) inhibitors and virtual screening based on it.
abstract: IκB kinase β (IKKβ) is an important anti-cancer target that plays crucial role in activating the transcription factor NF-κB in response to various inflammatory stimuli. In order to discover novel IKKβ inhibitors, a 3D chemical-feature-based QSAR pharmacophore model was established. A homology model of IKKβ enzyme was also developed to study the binding mode of IKKβ and its inhibitors. The two models were consistent in predicting the binding conformation of IKKβ inhibitor. Based on the virtual screening using the pharmacophore model, 16 compounds from SPECS database were selected after multiple filtrations for biological test. Two compounds with IC(50) values lower than 10 μM were discovered.
authors.affiliation: Key Laboratory of Carcinogenesis and Intervention of Jiangsu Province, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hao-Peng
authors.initials: HP
authors.lastname: Sun
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.forename: Fei-Hong
authors.initials: FH
authors.lastname: Chen
authors.forename: Sheng-Lie
authors.initials: SL
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D017386:Sequence Homology, Amino Acid
chemical_list: D008024:Ligands; D047428:Protein Kinase Inhibitors; D051550:I-kappa B Kinase