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AstraZeneca : Researchers at AstraZeneca Report Findings in Chemical Biology (Identification and Characterization of Dual Inhibitors of the USP25/28...

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12/07/2017 | 11:57pm CET

Researchers at AstraZeneca Report Findings in Chemical Biology (Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily)

By a News Reporter-Staff News Editor at Cancer Weekly -- Research findings on Life Science Research - Chemical Biology are discussed in a new report. According to news reporting originating from Cambridge, United Kingdom, by NewsRx correspondents, research stated, "The ubiquitin proteasome system is widely postulated to be a new and important field of drug discovery for the future, with the ubiquitin specific proteases (USPs) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the finding that USP28 is required for c-Myc stability suggests that USP28 inhibition may represent a novel approach to targeting this so far undruggable oncogene."

Our news editors obtained a quote from the research from AstraZeneca, "Here, we describe the discovery of the first reported inhibitors of USP28, which we demonstrate are able to bind to and inhibit USP28, and while displaying a dual activity against the closest homologue USP25, these inhibitors show a high degree of selectivity over other deubiquitinases (DUBs). The utility of these compounds as valuable probes to investigate and further explore cellular DUB biology is highlighted by the demonstration of target engagement against both USP25 and USP28 in cells. Furthermore, we demonstrate that these inhibitors are able to elicit modulation of both the total levels and the half-life of the c-Myc oncoprotein in cells and also induce apoptosis and loss of cell viability in a range of cancer cell lines. We however observed a narrow therapeutic index compared to a panel of tissue-matched normal cell lines."

According to the news editors, the research concluded: "Thus, it is hoped that these probes and data presented herein will further advance our understanding of the biology and tractability of DUBs as potential future therapeutic targets."

For more information on this research see: Identification and Characterization of Dual Inhibitors of the USP25/28 Deubiquitinating Enzyme Subfamily. Acs Chemical Biology, 2017;():. (American Chemical Society - www.acs.org; Acs Chemical Biology - www.pubs.acs.org/journal/acbcct)

The news editors report that additional information may be obtained by contacting J.D. Wrigley, Discovery Sciences, IMED Biotech Unit, AstraZeneca , Cambridge, UK. Additional authors for this research include G. Gavory, I. Simpson, M. Preston, H. Plant, J. Bradley, A.U. Goeppert, E. Rozycka, G. Davies, J. Walsh, A. Valentine, K. McClelland, K.E. Odrzywol, J. Renshaw, J. Boros, J. Tart, L. Leach, T. Nowak and R Ward (see also Life Science Research - Chemical Biology).

The direct object identifier (DOI) for that additional information is: https://doi.org/10.1021/acschembio.7b00334. This DOI is a link to an online electronic document that is either free or for purchase, and can be your direct source for a journal article and its citation.

Keywords for this news article include: Europe, Cambridge, United Kingdom, Chemical Biology, Drugs and Therapies, Life Science Research.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2017, NewsRx LLC

(c) 2017 NewsRx LLC, source Health Newsletters

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