• Title/Summary/Keyword: High-throughput Screening

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Advances in the Development and Validation of Test Methods in the United States

  • Casey, Warren M.
    • Toxicological Research
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    • v.32 no.1
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    • pp.9-14
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    • 2016
  • The National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) provides validation support for US Federal agencies and the US Tox21 interagency consortium, an interagency collaboration that is using high throughput screening (HTS) and other advanced approaches to better understand and predict chemical hazards to humans and the environment. The use of HTS data from assays relevant to the estrogen receptor signaling data pathway is used as an example of how HTS data can be combined with computational modeling to meet the needs of US agencies. As brief summary of US efforts in the areas of biologics testing, acute toxicity, and skin sensitization will also be provided.

Design, Syntheses and Biological Evaluations of Nonpeptidic Caspase 3 Inhibitors

  • Kim, Eun-Sook;Yoo, Sung-Eun;Yi, Kyu-Yang;Lee, Sun-Kyung;Noh, Jae-Sung;Jung, Yong-Sam;Kim, Eun-Hee;Jeong, Nak-Chul
    • Bulletin of the Korean Chemical Society
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    • v.23 no.7
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    • pp.1003-1010
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    • 2002
  • Caspase 3, a member of cysteine protease family, is well known as a major apoptosis effector and is involved in cell death as a result of ischemic diseases such as stroke and myocardial infarction, therefore the inhibition of caspase 3 may protect those apoptotic cell damages. During the high-throughput screening of the compounds from the Korea Chemical Bank, berberine derivatives (A and B), an isoquinoline alkaloid, have been identified as potential inhibitors for caspase 3. Based on this finding we carried out molecular modeling study to identify the pharmacophoric elements of berberine structure which interact with a substrate-recognition binding site of caspase 3 and came up with several novel scaffolds. In this report, we will discuss the molecular modeling, syntheses and the enzyme inhibitory activities of these novel compounds.

Label-Free and Real-Time Monitoring of Phosphatase Reactions Using a Phosphate-Specific and Fluorescent Probe

  • Lee, Ji-Hoon;Ahn, Hee-Chul;Shin, Dong-Yun;Ahn, Dae-Ro
    • Bulletin of the Korean Chemical Society
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    • v.29 no.5
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    • pp.943-947
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    • 2008
  • A phosphate-specific and fluorescent probe was prepared for label-free phosphatase assays based on fluorescence polarization. By using the probe, dephosphorylation reactions of DNA and protein substrates by calf intestinal alkaline phosphatase (CIP) could effectively be monitored in real-time. Since this assay method does not require additional materials such as labeled substrates and phosphospecific antibodies to obtain fluorescence polarization signals, it is simple, cost-effective, and expected to be useful not only for measuring activity of phosphatases but also for high-throughput screening of phosphatase inhibitors.

Development of Photo-sensor for Integrated Lab-On-a-Chip (집적화된 Lab-On-a Chip을 위한 광센서의 제작 및 특성 평가)

  • 김주환;신경식;김용국;김태송;김상식;주병권
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.17 no.4
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    • pp.404-409
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    • 2004
  • We fabricated photo-sensor for fluorescence detection in LOC. LOC is high throughput screening system. Our LOC screens biochemical reaction of protein using the immunoassay, and converts biochemical reaction into electrical signal using LIF(Laser Induced Fluorescence) detection method. Protein is labeled with rhodamine intercalating dye and finger PIN photodiode is used as photo-sensor We measured fluorescence emission of rhodamine dye and analyzed tendency of fluorescence detection, according to photo-sensor size, light intensity, and rhodamine concentration. Detection current was almost linearly proportional to two parameters, intensity and concentration, and was inversely proportional to photo-sensor size. Integrated LOC consists of optical-filter deposited photo-sensor and PDMS microchannel detected 50 (pg/${mu}ell$) rhodamine. For integrated LOC including light source, we used green LED as the light source and measured emitted fluorescence.

Review of Biological Network Data and Its Applications

  • Yu, Donghyeon;Kim, MinSoo;Xiao, Guanghua;Hwang, Tae Hyun
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.200-210
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    • 2013
  • Studying biological networks, such as protein-protein interactions, is key to understanding complex biological activities. Various types of large-scale biological datasets have been collected and analyzed with high-throughput technologies, including DNA microarray, next-generation sequencing, and the two-hybrid screening system, for this purpose. In this review, we focus on network-based approaches that help in understanding biological systems and identifying biological functions. Accordingly, this paper covers two major topics in network biology: reconstruction of gene regulatory networks and network-based applications, including protein function prediction, disease gene prioritization, and network-based genome-wide association study.

The Emergence of Behavioral Testing of Fishes to Measure Toxicological Effects

  • Brooks, Janie S.
    • Toxicological Research
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    • v.25 no.1
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    • pp.9-15
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    • 2009
  • Historically, research in toxicology has utilized non-human mammalian species, particularly rats and mice, to study in vivo the effects of toxic exposure on physiology and behavior. However, ethical considerations and the overwhelming increase in the number of chemicals to be screened has led to a shift away from in vivo work. The decline in in vivo experimentation has been accompanied by an increase in alternative methods for detecting and predicting detrimental effects: in vitro experimentation and in silico modeling. Yet, these new methodologies can not replace the need for in vivo work on animal physiology and behavior. The development of new, non-mammalian model systems shows great promise in restoring our ability to use behavioral endpoints in toxicological testing. Of these systems, the zebrafish, Danio rerio, is the model organism for which we are accumulating enough knowledge in vivo, in vitro, and in silico to enable us to develop a comprehensive, high-throughput toxicology screening system.

Natural Modulators of Estrogen Biosynthesis and Function as Chemopreventive Agents

  • Bhat, Krishna P.L.;Pezzuto, John M.
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.473-484
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    • 2001
  • There is clearly a need for novel breast cancer chemopreventive agents with enhanced potency and specificity with tittle or no side effects. To this end, several new chemical moieties have been synthesized or isolated from natural sources. In this reviewal we have described some agents currently in use or under development for treatment or prevention of breast cancer, as well as our own strategies for the discovery of natural product modulators of estrogen biosynthesis and function. In particulars bioassay-guided fractionation of active plant extracts is a unique method for identifying agents with novel mechanisms of action, some of which should be useful for prevention of human cancer. Further, with the advent of combinatorial chemistry and high throughput screening, even greater progress may now be expected with natural product leads.

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Genotoxicity Study of sophoricoside derivatives in mammalian cells system

  • Yun, Hye-Jung;Kim, Youn-Jung;Kim, Eun-Young;Kim, Young-Soo;Kim, Mi-Kyung;Lee, Seung-Ho;Jung, Sang-Hun;Ryu, Jae-Chun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.178.2-178.2
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    • 2003
  • To develope the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, JSH-Ⅵ-3, JSH-Ⅶ-3, and JSH-Ⅷ-3 were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of Quantity. Mouse lymphoma thymidine kinase ($tk^{+/-}$) gene assay(MOLY) and single cell gel electrophoresis (Comet) assay in mammalian cells were used as HTTS tool in our laboratory. (omitted)

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The Role of Korea Chemical Bank in "Hit to Lead" process of Drug Discovery

  • Kim, Sun-Woo;Kim, Dong-Wook;Kim, Sun-Ho;Choi, Yeon-Joo;Kim, Joo-Young;Han, Mi-Jung;Kim, Oke-Kil;Kil, Kyong-Ok;Kim, Sung-Soo
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.249.1-249.1
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    • 2003
  • The Korea Chemical Bank (KCB) has more than 80,000 compound collections. provided from many companies, academies and institutes. KCB has supported high-throughput screening (HTS) against 80 biological targets and identified a number of hits over 20 targets. These hits were first validated by confirming the purity and novelty of anticipated compound. We also determined their physiochemical properties. (omitted)

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