title: The first pharmacophore model for potent NF-kappaB inhibitors.
abstract: As an important transcription factor of the Ral family, nuclear factor-kappa B (NF-kappaB) is involved in numerous cellular processes, such as the responses to cellular stress and to inflammation. For better elucidating the quantitative structure-activity relationship of NF-kappaB inhibitors and determining possible ligand-protein interaction, a pharmacophore model, Hypo1, was built based on 35 training molecules by Catalyst/HypoGen algorithm. The five pharmacophore features of Hypo1, including three hydrophobic groups, one hydrogen-bond acceptor, and one hydrophobic aromatic group, were correctly mapped onto NF-kappaB surface. This model has strong capability to identify NF-kappaB inhibitors and to predict the activities of structurally diverse molecules, thus to provide a valuable tool in the design of new leads with desired biological activity by virtual screening.
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Teng
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Shao
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Nai-Wan
authors.initials: NW
authors.lastname: Hsiao
mesh_terms: D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D008024:Ligands; D008956:Models, Chemical; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D008024:Ligands; D016328:NF-kappa B