title: Searching therapeutic agents for treatment of Alzheimer disease using the Monte Carlo method.
abstract: Quantitative structure - activity relationships (QSARs) for the pIC50 (binding affinity) of gamma-secretase inhibitors can be constructed with the Monte Carlo method using CORAL software (http://www.insilico.eu/coral). The considerable influence of the presence of rings of various types with respect to the above endpoint has been detected. The mechanistic interpretation and the domain of applicability of the QSARs are discussed. Methods to select new potential gamma-secretase inhibitors are suggested.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Universita' degli Studi di Milano, Via L. Mangiagalli, 25, 20133 Milan, Italy.
authors.forename: Mariya A
authors.initials: MA
authors.lastname: Toropova
authors.affiliation: IRCCS, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via La Masa 19, Milano 20156, Italy. Electronic address: andrey.toropov@marionegri.it.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Toropov
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 1, 12808 Prague 2, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Raška
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 1, 12808 Prague 2, Czech Republic.
authors.forename: Mária
authors.initials: M
authors.lastname: Rašková
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009010:Monte Carlo Method; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D053829:Amyloid Precursor Protein Secretases
keywords: CORAL software; Gamma-secretase inhibitor; Monte Carlo method; OECD principles; QSAR