Kwon, Y-JLee, WGenovesio, AEmans, N2013-01-302013-01-302012-03Kwon, Y-J, Lee, W, Genovesio, A and Emans, N. 2012. A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs. Journal of Biomolecular Screening, vol. 17(3), pp 379-851087-0571http://jbx.sagepub.com/content/early/2011/11/15/1087057111427347http://hdl.handle.net/10204/6498Copyright: 2012 SAGE Publications. This is an ABSTRACT ONLY. The definitive version is published in Journal of Biomolecular Screening, vol. 17(3), pp 379-85G-protein–coupled receptors (GPCRs) are pivotal in cellular responses to the environment and are common drug targets. Identification of selective small molecules acting on single GPCRs is complicated by the shared machinery coupling signal transduction to physiology. Here, the authors demonstrate a high-content screen using a panel of GPCR assays to identify receptor selective molecules acting within the kinase/phosphatase inhibitor family. A collection of 88 kinase and phosphatase inhibitors was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping endocytosis or disrupting internalization of multiple receptors. They identified compounds acting on a sole GPCR from activities in a broad range of chemical structures that could not be easily sorted by conventional means. Selective analysis can therefore rapidly select compounds selectively affecting GPCR activity with specificity to one receptor class through high-content screening.enHigh-content screeningG-protein–coupled receptorEndocytosisCell-based assayImage analysisChemical biologyArticleKwon, Y., Lee, W., Genovesio, A., & Emans, N. (2012). A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs. http://hdl.handle.net/10204/6498Kwon, Y-J, W Lee, A Genovesio, and N Emans "A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs." (2012) http://hdl.handle.net/10204/6498Kwon Y, Lee W, Genovesio A, Emans N. A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs. 2012; http://hdl.handle.net/10204/6498.TY - Article AU - Kwon, Y-J AU - Lee, W AU - Genovesio, A AU - Emans, N AB - G-protein–coupled receptors (GPCRs) are pivotal in cellular responses to the environment and are common drug targets. Identification of selective small molecules acting on single GPCRs is complicated by the shared machinery coupling signal transduction to physiology. Here, the authors demonstrate a high-content screen using a panel of GPCR assays to identify receptor selective molecules acting within the kinase/phosphatase inhibitor family. A collection of 88 kinase and phosphatase inhibitors was screened against seven agonist-induced GPCR internalization cell models as well as transferrin uptake in human embryonic kidney cells. Molecules acting on a single receptor were identified through excluding pan-specific compounds affecting housekeeping endocytosis or disrupting internalization of multiple receptors. They identified compounds acting on a sole GPCR from activities in a broad range of chemical structures that could not be easily sorted by conventional means. Selective analysis can therefore rapidly select compounds selectively affecting GPCR activity with specificity to one receptor class through high-content screening. DA - 2012-03 DB - ResearchSpace DP - CSIR KW - High-content screening KW - G-protein–coupled receptor KW - Endocytosis KW - Cell-based assay KW - Image analysis KW - Chemical biology LK - https://researchspace.csir.co.za PY - 2012 SM - 1087-0571 T1 - A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs TI - A high-content subtractive screen for selecting small molecules affecting internalization of GPCRs UR - http://hdl.handle.net/10204/6498 ER -