The first pharmacophore model for potent NF-kappaB inhibitors.

TitleThe first pharmacophore model for potent NF-kappaB inhibitors.
Publication TypeJournal Article
Year of Publication2009
AuthorsTsai K-C, Teng L-W, Shao Y-M, Chen Y-C, Lee Y-C, Li M, Hsiao N-W
JournalBioorg Med Chem Lett
Volume19
Issue19
Pagination5665-9
Date Published2009 Oct 1
ISSN1464-3405
KeywordsBinding Sites, Combinatorial Chemistry Techniques, Computer Simulation, Ligands, Models, Chemical, NF-kappa B, Quantitative Structure-Activity Relationship, Software
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.

DOI10.1016/j.bmcl.2009.08.021
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/19726185?dopt=Abstract
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID19726185