The first pharmacophore model for potent NF-kappaB inhibitors.
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.
Tsai
Keng-Chang
KC
Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
Teng
Li-Wei
LW
Shao
Yi-Ming
YM
Chen
Yu-Chen
YC
Lee
Yu-Ching
YC
Li
Minyong
M
Hsiao
Nai-Wan
NW
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
D008024:Ligands; D016328:NF-kappa B