title: Data-driven approaches used for compound library design, hit triage and bioactivity modeling in high-throughput screening.
abstract: High-throughput screening (HTS) campaigns are routinely performed in pharmaceutical companies to explore activity profiles of chemical libraries for the identification of promising candidates for further investigation. With the aim of improving hit rates in these campaigns, data-driven approaches have been used to design relevant compound screening collections, enable effective hit triage and perform activity modeling for compound prioritization. Remarkable progress has been made in the activity modeling area since the recent introduction of large-scale bioactivity-based compound similarity metrics. This is evidenced by increased hit rates in iterative screening strategies and novel insights into compound mode of action obtained through activity modeling. Here, we provide an overview of the developments in data-driven approaches, elaborate on novel activity modeling techniques and screening paradigms explored and outline their significance in HTS.
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom.|Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, The Netherlands.
authors: Shardul
authors: S
authors: Paricharak
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom.|Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City, Mexico.
authors: Oscar
authors: O
authors: Méndez-Lucio
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom.
authors: Aakash
authors: A
authors: Chavan Ravindranath
authors: Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom.
authors: Andreas
authors: A
authors: Bender
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, The Netherlands.
authors: Adriaan P
authors: AP
authors: IJzerman
authors: Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University, RA Leiden, The Netherlands.
authors: Gerard J P
authors: GJP
authors: van Westen
mesh_terms: D000818:Animals; D003625:Data Collection; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008958:Models, Molecular; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D054852:Small Molecule Libraries