title: Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF-κB.
abstract: Ulcerative colitis and Crohn's disease are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract. Nuclear Factor Kappa B (NF-κB) is a transcription factor that plays a key role in regulating expression of multiple inflammatory and immune genes. In this study, a Topological Virtual Screening study has been carried out to achieve a model capable of finding new compounds active in ulcerative colitis by inhibiting NF-κB. Different topological indices were used as structural descriptors, and their relation to biological activity was determined using linear discriminant analysis. A topological model consisting of two discriminant functions was built up. The first function focused in the discrimination between NF-κB active and inactive compounds, and the second one in distinguishing between compounds active and inactive on ulcerative colitis. The model was then applied sequentially to a large database of compounds with unknown activity. Twenty-eight of such compounds were predicted to be active and selected for in vitro and in vivo testing.
authors: Molecular Connectivity and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avda. VA Estellés, s/n, 46100 Burjassot, Valencia, Spain.
authors: María
authors: M
authors: Gálvez-Llompart
authors: María C
authors: MC
authors: Recio
authors: Ramón
authors: R
authors: García-Domenech
mesh_terms: D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D019295:Computational Biology; D004353:Drug Evaluation, Preclinical; D008962:Models, Theoretical; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009930:Organic Chemicals / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D016328:NF-kappa B; D009930:Organic Chemicals