Impact of high-throughput screening in biomedical research

Macarrόn, Ricardo; Banks, Martyn; Bojanic, Dejan; Burns, David J.; Cirovic, Dragan A.; Garyantes, Tina; Green, Darren V. S.; Hertzberg, Robert; Janzen, William P.; Paslay, Jeff W.; Schopfer, Ulrich; Sittampalam, G. Sitta

doi:10.1038/nrd3368

Cited by 1,092 publications

(915 citation statements)

References 56 publications

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“…With developments in modern science and technology, isolation of bioactive components from natural sources and identification of their molecular mechanism of action in the living system became an important pharmacological research [8][9][10]. Several promising natural products and natural product-inspired compounds are currently in clinical and pre-clinical developmental stages for cancer treatment [7,[11][12][13]. Limited supply of active compounds from natural sources, difficulties in complete profiling of their cellular targets and characterization of their molecular mechanisms of Phytochemicals and their synthetic derivatives are making a significant contribution in modern drug discovery programs by targeting several human diseases, including cancer.…”

Section: Introductionmentioning

confidence: 99%

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Prasannan

Kalesh

Shanmugam

et al. 2012

Biochemical Pharmacology

126

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Section: Introductionmentioning

confidence: 99%

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Prasannan

Kalesh

Shanmugam

et al. 2012

Biochemical Pharmacology

126

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“…Although high-throughput screening using libraries of compounds is a proven way to identify novel entities [64], these highly artificial and non-physiological assay systems have low success rates. Moreover, this process is time-consuming and sample-intensive.…”

Section: Discussionmentioning

confidence: 99%

Bringing single-molecule spectroscopy to macromolecular protein complexes

Joo

Fareh

Kim

2013

Trends in Biochemical Sciences

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Single-molecule fluorescence spectroscopy offers real-time, nanometer-resolution information. Over the past two decades, this emerging single-molecule technique has been rapidly adopted to investigate the structural dynamics and biological functions of proteins. Despite this remarkable achievement, single-molecule fluorescence techniques must be extended to macromolecular protein complexes that are physiologically more relevant for functional studies. In this review, we present recent major breakthroughs for investigating protein complexes within cell extracts using single-molecule fluorescence. We outline the challenges, future prospects and potential applications of these new single-molecule fluorescence techniques in biological and clinical research. Single-molecule protein studiesSingle-molecule techniques have become potent tools for the discovery of novel protein mechanisms by allowing high spatiotemporal resolution. Sub-nanometer resolution, the ultimate scale of biological systems, has been reached with single-molecule fluorescence microscopy[1] and spectroscopy [2]; single-molecule force and torque spectroscopy [3,4]; atomic force microscopy [5] and spectroscopy [6]; and nanopores [7]. Measurements can be carried out on the biologically relevant time scales of microseconds to minutes.Among these techniques, single-molecule fluorescence spectroscopy has enabled researchers to unveil the action mechanism of a protein by imaging protein activity in real time. Benefitting from advances in general microscopy[1], detection devices [8], and fluorophore physics [9,10], single-molecule fluorescence spectroscopy has reached sub-nanometer spatial resolution [11] and microsecond temporal resolution [12,13]. Single-molecule fluorescence imaging is carried out primarily with total internal reflection, confocal, and zero-mode waveguide microscopy [2]. Among these, total internal reflection fluorescence microscopy has been employed by several research teams in the development of novel techniques described in this review [14][15][16][17] Single-molecule observations using cell extractsUnlike purified recombinant proteins, crude cell extracts provide more biologically relevant environment in which molecules of interest can interact not only with their partners but also with other cellular components. It was anticipated to combine this approach with single molecule techniques and observe the assembly and function of macromolecular complexes in real time. However, technical hurdles related to the specificity and efficiency of labeling molecules of interest within crude cell extracts had been reported [22][23][24]. In order to overcome this limitation, several groups recently developed original approaches. Hoskins et al. used protein complexes specifically tagged with fluorophores [14,19], and Yardimci et al. immunostained reaction products using specific fluorescent antibodies [15,20]. Real-time observation of spliceosome assemblyDespite the relatively small number of genes in the human genome, we have extraordin...

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“…Les « big pharma » ont souvent eu recours aux deux stratégies. Le criblage de chimiothèques est largement utilisé dans l'industrie pharmaceutique dans le but d'accélérer la découverte de drogues [2,9] (➜) Dans le monde académique, le criblage n'a pas la même vocation.…”

Section: Naissance Des Chimiothèques Académiques Françaisesunclassified

Chimiothèque Nationale

Mahuteau-Betzer

2015

Med Sci (Paris)

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> La Chimiothèque Nationale (CN) est une fédé-ration de chimiothèques académiques locales, une chimiothèque étant une collection de petites molécules de synthèse ou isolées de produits naturels. Une « extractothèque » contenant des extraits naturels est aussi proposée. La force de la Chimiothèque Nationale réside dans la diversité de sa collection et la possibilité de proposer des interlocuteurs chimistes aux biologistes cribleurs. Les collaborations post-criblage permettent, à travers la synthèse d'analogues et d'outils chimiques, d'identifier de nouvelles sondes chimiques pour comprendre le vivant et, dans certains cas, d'envisager des applications dans le domaine thérapeutique. Dans cet article, nous montrerons les avancées et les perspectives que cette fédération a permis d'engendrer. > S'il peut faciliter dans certains cas la découverte de molécules susceptibles d'avoir des applications thérapeutiques, il vise surtout à l'identification de sondes précieuses pour étudier le vivant en modulant ou contrôlant une activité biologique. En effet, la petite molécule identifiée par criblage, nommée « touche », facilite l'étude de la nouvelle cible. Lorsque le criblage est enzymatique, la petite molécule permet de valider la fonction biologique de cette enzyme. Lorsque le criblage est phénotypique, elle peut permettre d'identifier la cible [3].

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Impact of high-throughput screening in biomedical research

Cited by 1,092 publications

References 56 publications

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Key cell signaling pathways modulated by zerumbone: Role in the prevention and treatment of cancer

Bringing single-molecule spectroscopy to macromolecular protein complexes

Chimiothèque Nationale

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