title: Toward in silico structure-based ADMET prediction in drug discovery.
abstract: Quantitative structure-activity relationship (QSAR) methods and related approaches have been used to investigate the molecular features that influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. As the three-dimensional structures of several major ADMET proteins become available, structure-based (docking-scoring) computations can be carried out to complement or to go beyond QSAR studies. Applying docking-scoring methods to ADMET proteins is a challenging process because they usually have a large and flexible binding cavity; however, promising results relating to metabolizing enzymes have been reported. After reviewing current trends in the field we applied structure-based methods in the context of receptor flexibility in a case study involving the phase II metabolizing sulfotransferases. Overall, the explored concepts and results suggested that structure-based ADMET profiling will probably join the mainstream during the coming years.
authors: Inserm UMR-S 973, Molécules Thérapeutiques In Silico, Université Paris Diderot, Sorbonne Paris Cité, 35 Rue Helene Brion, 75013 Paris, France.
authors: Gautier
authors: G
authors: Moroy
authors: Virginie Y
authors: VY
authors: Martiny
authors: Philippe
authors: P
authors: Vayer
authors: Bruno O
authors: BO
authors: Villoutreix
authors: Maria A
authors: MA
authors: Miteva
mesh_terms: D000042:Absorption; D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D010600:Pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations