Origin and evolution of high throughput screening

Pereira, Dennis; Williams, John A.

doi:10.1038/sj.bjp.0707373

Cited by 296 publications

(209 citation statements)

References 19 publications

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“…Biotechnology has established itself as an "industry" dedicated to drug discovery and its success is evident when one observes its use for these kind of activity (Drews, 2000, Hopkins et al 2007Pereira and Williams, 2007). The adaptation of biotechnology to this type of activity was successful, especially, regarding the technology and knowledge appropriation conducted by large pharmaceutical companies.…”

Section: Drug Discovery Afterbiotechnologymentioning

confidence: 99%

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Technical Change and the Incorporation of Biotechnology in the Pharmaceutical Industry

Matos¹,

Queiroz²

2017

Blucher Engineering Proceedings

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Resumo:A indústria farmacêutica, ao longo de sua história, tem enfrentado inúmeras mudanças e desafios. Atualmente o setor passa por uma crise de produtividade em suas atividades de P&D. Este fato coloca uma série de questionamentos importantes, para o escopo deste estudo destacam-se dois: Como a indústria tem lidado com esta crise? As atitudes do setor trazem novas mudanças ou dinâmicas a este mesmo? A resposta que este artigo propõe é também o argumento que se procura defender, que é: a solução tentada pela indústria farmacêutica é tanto tecnológica quanto organizacional e esta solução reside fora das fronteiras da firma, sendo assim, as grandes empresas farmacêuticas estão usando estratégias, especialmente as aquisições de pequenas empresas de biotecnologia, para incorporar novas tecnologias que, em tese, vão aumentar a taxa inovativa das grandes empresas. Para se conseguir o objetivo proposto, este trabalho propõe combinar uma pesquisa bibliográfica focada na literatura econômica e na literatura especializada nas técnicas usadas para se desenvolver novas drogas para que se observe a evolução das atividades de P&D. Ademais, alguns dados importantes serão apresentados para sustentar algumas afirmações. Como conclusão, o artigo mostra que a evolução das atividades de P&D criou uma necessidade, nas grandes empresas farmacêuticas, que fez a incorporação de pequenas empresas de biotecnologia uma estratégia recorrente.Palavras-chave: biotecnologia, indústria farmacêutica, mudança técnica, competências, aquisições Área Temática: 5.8 Inovação, competências e Competitividade JEL: O33, L22, L65 Abstract:The pharmaceutical industry has undergone several changes and challenges, nowadays the industry is facing a R&D productivity crises. A series of questions arise from this fact, two of it can be highlighted as important for this study that are: how the industry is dealing with this crises? Does it bring new features to the sector? The answer that this article proposes it is also our argument, that is: the solution sought by the industry is both technological and organizational and it resides outside the large pharmaceutical enterprise's borders, therefore, those companies are using strategies, especially acquisitions of small biotech enterprises to incorporate new technologies that, arguably, will increase the large enterprise's innovative output. Therefore this article objective is to prove the argument. In order to achieve the objective proposed this work proposes to combine bibliographic research on the economic literature and the specialized literature on drug discovery techniques to describe this activity evolution, in addition, some important data will be present to sustain the assertions made. As a conclusion the article shows that the R&D activities evolution has created a biotechnology trajectory, in the pharmaceutical companies, that made the incorporation of small biotech enterprises a recurrent strategy.

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Section: Drug Discovery Afterbiotechnologymentioning

confidence: 99%

“…The High Throughput Screening (HTS) is one of the most prominent biotechnology and it has increased, significantly, the capacity of enterprises to screen new compounds through patronization and automatization (Nigtingale, 2000;Pereira and Williams, 2007).…”

Section: Drug Discovery Afterbiotechnologymentioning

confidence: 99%

Technical Change and the Incorporation of Biotechnology in the Pharmaceutical Industry

Matos¹,

Queiroz²

2017

Blucher Engineering Proceedings

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“…High-throughput screening (HTS) has developed over the last 2 decades as the principal method of lead identification in drug discovery (20). With advances in molecular biology and genomics, target-based screens, which detect small modulators of proteins, have overtaken traditional phenotypic screens in HTS applications (21).…”

Section: T He Cyclic-amp Response Element Binding (Creb) Proteinmentioning

confidence: 99%

Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory

Xia

Huang

Guo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Many studies have implicated the cAMP Response Element Binding (CREB) protein signaling pathway in long-term memory. To identify small molecule enhancers of CREB activation of gene expression, we screened Ϸ73,000 compounds, each at 7-15 concentrations in a quantitative high-throughput screening (qHTS) format, for activity in cells by assaying CREB mediated ␤-lactamase reporter gene expression. We identified 1,800 compounds that potentiated CREB mediated gene expression, with potencies as low as 16 nM, comprising 96 structural series. Mechanisms of action were systematically determined, and compounds that affect phosphodiesterase 4, protein kinase A, and cAMP production were identified, as well as compounds that affect CREB signaling via apparently unidentified mechanisms. qHTS folowed by interrogation of pathway targets is an efficient paradigm for lead generation for chemical genomics and drug development. memory enhancer ͉ phosphodiesterase inhibitor ͉ quantitative high-throughput screening

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“…It has been the mainstay for lead identification in the pharmaceutical industry for the past two decades (Pereira & Williams, 2007;Macarron et al, 2011). Typically, 10 000 compounds are screened per day to identify hits that show a therapeutic response, with hit compounds being progressed into hit-to-lead development.…”

Section: Introductionmentioning

confidence: 99%

The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design

Rawson

McPhillie

Johnson

et al. 2017

Acta Cryst Sect D Struct Biol

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Recent developments in electron microscopy (EM) have led to a step change in our ability to solve the structures of previously intractable systems, especially membrane proteins and large protein complexes. This has provided new opportunities in the field of structure-based drug design, with a number of highprofile publications resolving the binding sites of small molecules and peptide inhibitors. There are a number of advantages of EM over the more traditional X-ray crystallographic approach, such as resolving different conformational states and permitting the dynamics of a system to be better resolved when not constrained by a crystal lattice. There are still significant challenges to be overcome using an EM approach, not least the speed of structure determination, difficulties with low-occupancy ligands and the modest resolution that is available. However, with the anticipated developments in the field of EM, the potential of EM to become a key tool for structure-based drug design, often complementing X-ray and NMR studies, seems promising.

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Origin and evolution of high throughput screening

Cited by 296 publications

References 19 publications

Technical Change and the Incorporation of Biotechnology in the Pharmaceutical Industry

Technical Change and the Incorporation of Biotechnology in the Pharmaceutical Industry

Identification of compounds that potentiate CREB signaling as possible enhancers of long-term memory

The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design

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