Download A Practical Guide to Assay Development and High-Throughput by Taosheng Chen PDF

By Taosheng Chen

ISBN-10: 1420070509

ISBN-13: 9781420070507

The improvement of compatible assays, the mixing of applicable know-how, and the powerful administration of the basic infrastructure are all serious to the good fortune of any high-throughput screening (HTS) pastime. besides the fact that, few scientists have the multidisciplinary adventure had to keep an eye on all points of an HTS drug discovery venture. a realistic advisor to Assay improvement and High-Throughput Screening in Drug Discovery integrates the event of numerous specialists who provide basic and functional counsel throughout quite a few occasions. The ebook first discusses assay advancements for vital goal sessions comparable to protein kinases and phosphatases, proteases, nuclear receptors, G protein-coupled receptors, ion channels, and warmth surprise proteins. It subsequent examines assay advancements for cellphone viability, apoptosis, and infectious ailments. The participants discover the applying of rising applied sciences and structures, together with image-based excessive content material screening, RNA interference, and first cells. eventually, they speak about the fundamental parts of the built-in HTS approach, akin to screening automation, compound library administration, the screening of typical items from botanical resources, and screening informatics. Designed to encourage researchers to convey extra advances to the sector, this quantity offers sensible information on how one can start up, validate, optimize, and deal with a bioassay meant to monitor huge collections of compounds. Drawing at the wisdom from specialists actively considering assay improvement and HTS, it is a source that's either complete and targeted.

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Extra info for A Practical Guide to Assay Development and High-Throughput Screening in Drug Discovery (Critical Reviews in Combinatorial Chemistry)

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Et al. 2003. A widely applicable, high-throughput TR-FRET assay for the measurement of kinase autophosphorylation: VEGFR-2 as a prototype. J. Biomol. Screen. 8, 447–452. Newman, M. and S. Josiah. 2004. Utilization of fluorescence polarization and time resolved fluorescence resonance energy transfer assay formats for SAR studies: Src kinase as a model system. J. Biomol. Screen. 9, 525–532. Nickischer, D. et al. 2006. Development and implementation of three mitogen-activated protein kinase (MAPK) signaling pathway imaging assays to provide MAPK module selectivity profiling for kinase inhibitors.

Et al. 1998. Synthesis of fluorescent substrates for protein tyrosine phosphatase assays. Bioorg. Med. Chem. Lett. 8, 1301–1302. , Y. N. Hodge. 2003. Determining appropriate substrate conversion for enzymatic assays in high-throughput screening. J. Biomol. Screen. 8, 694–700. D. R. Oldenburg. 1999. A simple statistical parameter for use in evaluation and validation of high-throughput screening assays. J. Biomol. Screen. 4, 67–73. L. et al. 2007. An enzyme-linked immunosorbent assay to measure insulin receptor dephosphorylation by PTP1B.

The presence of “promiscuous” inhibitors or “aggregating” compounds in a chemical library has become a recent area of research. These compounds can cause false positives that can be reduced with certain detergents and can frequently be recognized by steep concentration response curves or enzyme concentration-dependent shifts in the IC50 (Feng and Shoichet, 2006; Shoichet, 2006). The exact mechanism of these false positives is not known but it is possible that these compounds induce the formation of compound–enzyme clusters that reduce enzyme activity.

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