Application of High-throughput Screening Techniques to Drug Discovery

Cox, Brian J.; Merritt, Andy; Binnie, Alastair; Donnelly, M.; Mander, Tom; Denyer, Jane; Evans, Brian; Green, Darren V. S.; Lewis, Jane A; Valler, Martin J.; Watson, Stephen P.

doi:10.1016/s0079-6468(08)70058-4

Cited by 71 publications

(29 citation statements)

References 59 publications

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“…1 Although electrophysiological methods are definitive for characterizing channels and modulators, the extremely low throughput precludes their use in highthroughput screening (HTS), in which compound libraries consisting of thousands to millions of discrete chemical entities are tested for binding to or modification of function of the target. 2,3 Optical methods are well suited to HTS assays, due to their speed, low cost, and ability to perform multiple experiments in parallel.…”

Section: Odern Approaches For Ion Channel Drug Screen-mentioning

confidence: 99%

pH-Insensitive FRET Voltage Dyes

Maher¹,

Wu²,

Ao³

2007

SLAS Discovery

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Many high-throughput ion channel assays require the use of voltage-sensitive dyes to detect channel activity in the presence of test compounds. Dye systems employing Förster resonance energy transfer (FRET) between 2 membrane-bound dyes are advantageous in combining high sensitivity, relatively fast response, and ratiometric output. The most widely used FRET voltage dye system employs a coumarin fluorescence donor whose excitation spectrum is pH dependent. The authors have validated a new class of voltage-sensitive FRET donors based on a pyrene moiety. These dyes are significantly brighter than CC2-DMPE and are not pH sensitive in the physiological range. With the new dye system, the authors demonstrate a new high-throughput assay for the acid-sensing ion channel (ASIC) family. They also introduce a novel method for absolute calibration of voltagesensitive dyes, simultaneously determining the resting membrane potential of a cell. (Journal of Biomolecular Screening 2007:656-667)

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Section: Odern Approaches For Ion Channel Drug Screen-mentioning

confidence: 99%

pH-Insensitive FRET Voltage Dyes

Maher¹,

Wu²,

Ao³

2007

SLAS Discovery

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“…(1) The well data view corresponds to four-marker data from physical sample wells. (2) The formulation data view collates information from all markers used in the experiment and associates it with each combinatorial treatment. (3) The normalized data view handles variability in sample readings across plates by comparing the treatment response of a sample with that of untreated, stained wells (negative controls) on each plate.…”

Section: Data Processingmentioning

confidence: 99%

“…Three individually successful techniques in the fields of biotechnology and drug discovery are high-throughput (HT) screening platforms (1), flow cytometry (2)(3)(4), and data-mining tools, such as hierarchical clustering (5)(6)(7)(8). In this study, these three techniques have been combined and used successfully to detect cell states induced by multifactor combinations.…”

mentioning

confidence: 99%

Combination of automated high throughput platforms, flow cytometry, and hierarchical clustering to detect cell state

et al. 2007

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Background: This study examined whether hierarchical clustering could be used to detect cell states induced by treatment combinations that were generated through automation and high-throughput (HT) technology. Data-mining techniques were used to analyze the large experimental data sets to determine whether nonlinear, non-obvious responses could be extracted from the data. Methods: Unary, binary, and ternary combinations of pharmacological factors (examples of stimuli) were used to induce differentiation of HL-60 cells using a HT automated approach. Cell profiles were analyzed by incorporating hierarchical clustering methods on data collected by flow cytometry. Data-mining techniques were used to explore the combinatorial space for nonlinear, unexpected events. Additional small-scale, follow-up experiments were performed on cellular profiles of interest. Results: Multiple, distinct cellular profiles were detected using hierarchical clustering of expressed cell-surface antigens. Data-mining of this large, complex data set

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“…dústria farmacêutica, que faz pesquisa, após a evolução da química combinatória e o advento de métodos robotizados de avaliação da afinidade de coleções de candidatos de ligantes de alvos macromoleculares 11 (e.g. "HTS, high throughput screening").…”

Section: Figura 1 Cronologia Do Processo De Descoberta De Fármacosunclassified

A questão da inovação em fármacos no Brasil: proposta de criação do programa nacional de fármacos (Pronfar)

Barreiro¹,

Fraga²

2005

Quím. Nova

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Application of High-throughput Screening Techniques to Drug Discovery

Cited by 71 publications

References 59 publications

pH-Insensitive FRET Voltage Dyes

pH-Insensitive FRET Voltage Dyes

Combination of automated high throughput platforms, flow cytometry, and hierarchical clustering to detect cell state

A questão da inovação em fármacos no Brasil: proposta de criação do programa nacional de fármacos (Pronfar)

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