Plate-based diversity subset screening generation 2: an improved paradigm for high-throughput screening of large compound files

Autor: James Edward John Mills, Robert E. Sharp, Joe Bradley, Jens Loesel, Marie-Claire Peakman, Christine Williams, David McLoughlin, Jeremy R. Everett, Hongyao Zhu, Andrew Simon Bell
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
SELECTION
Selection (relational algebra)
Computer science
Chemistry
Multidisciplinary
Drug Evaluation
Preclinical
Chemistry
Medicinal
computer.software_genre
2nd Generation
High-throughput screening (HTS)
Screening file
DESIGN
Drug Discovery
QD
Pharmacology & Pharmacy
Ro40
Lead discovery
OF-THE-ART
Diversity
PRODUCTIVITY
Drug discovery
RESEARCH-AND-DEVELOPMENT
Rule of 40
General Medicine
CHEMICAL DIVERSITY
Chemistry
Applied
Chemistry
Physical Sciences
Original Article
Data mining
Life Sciences & Biomedicine
Algorithms
Information Systems
Biochemistry & Molecular Biology
EFFICIENCY
High-throughput screening
DRUG-DISCOVERY
Nanotechnology
Catalysis
Inorganic Chemistry
Small Molecule Libraries
03 medical and health sciences
Subset
High-Throughput Screening Assays
Computer Simulation
Physical and Theoretical Chemistry
Molecular Biology
Plate-based
Science & Technology
Organic Chemistry
Reproducibility of Results
IN-VITRO
Chemical space
030104 developmental biology
Biological target
Chemical diversity
computer
Zdroj: Molecular Diversity
ISSN: 1381-1991
Popis: High-throughput screening (HTS) is an effective method for lead and probe discovery that is widely used in industry and academia to identify novel chemical matter and to initiate the drug discovery process. However, HTS can be time consuming and costly and the use of subsets as an efficient alternative to screening entire compound collections has been investigated. Subsets may be selected on the basis of chemical diversity, molecular properties, biological activity diversity or biological target focus. Previously, we described a novel form of subset screening: plate-based diversity subset (PBDS) screening, in which the screening subset is constructed by plate selection (rather than individual compound cherry-picking), using algorithms that select for compound quality and chemical diversity on a plate basis. In this paper, we describe a second-generation approach to the construction of an updated subset: PBDS2, using both plate and individual compound selection, that has an improved coverage of the chemical space of the screening file, whilst only selecting the same number of plates for screening. We describe the validation of PBDS2 and its successful use in hit and lead discovery. PBDS2 screening became the default mode of singleton (one compound per well) HTS for lead discovery in Pfizer. Electronic supplementary material The online version of this article (doi:10.1007/s11030-016-9692-9) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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