{"id":46391,"date":"2020-09-29T11:01:36","date_gmt":"2020-09-29T09:01:36","guid":{"rendered":"https:\/\/aktuelles.uni-frankfurt.de\/?p=46391"},"modified":"2023-02-22T14:18:25","modified_gmt":"2023-02-22T13:18:25","slug":"a-cancer-shredder-substance-with-new-mechanism-of-action-found","status":"publish","type":"post","link":"https:\/\/aktuelles.uni-frankfurt.de\/en\/english\/a-cancer-shredder-substance-with-new-mechanism-of-action-found\/","title":{"rendered":"A cancer shredder: substance with new mechanism of action found"},"content":{"rendered":"<div class=\"wp-block-image\"><figure class=\"aligncenter size-full\"><img fetchpriority=\"high\" decoding=\"async\" width=\"650\" height=\"450\" src=\"https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2020\/09\/beitragsbild_Comic_PROTAC_DEU-2.jpg\" alt=\"\" class=\"wp-image-46389\" srcset=\"https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2020\/09\/beitragsbild_Comic_PROTAC_DEU-2.jpg 650w, https:\/\/aktuelles.uni-frankfurt.de\/wp-content\/uploads\/2020\/09\/beitragsbild_Comic_PROTAC_DEU-2-300x208.jpg 300w\" sizes=\"(max-width: 650px) 100vw, 650px\" \/><figcaption>The PROTAC substance tears out the \u2018Aurora\u2019 pages which the tumour needs and destroys them. (Copyright: Dr. Sandy Pernitzsch)<\/figcaption><\/figure><\/div>\n\n\n\n<p><strong><em>Researchers at Goethe University Frankfurt and the university of W\u00fcrzburg have developed a new compound for treating cancer. It destroys a protein that triggers its development.<\/em><\/strong><\/p>\n\n\n\n<p>The villain in this drama has a pretty name: Aurora \u2013 Latin for dawn. In the world of biochemistry, however, Aurora (more precisely: Aurora-A kinase) stands for a protein that causes extensive damage. There, it has been known for a long time that Aurora often causes cancer. It triggers the development of leukemias and many pediatric cancers, such as neuroblastomas.<\/p>\n\n\n\n<p>Researchers at the universities of Frankfurt and W\u00fcrzburg have now developed a drug that can disarm Aurora. Stefan Knapp, Professor of Pharmaceutical Chemistry at Goethe University Frankfurt, and Dr. Elmar Wolf, biochemist and research group leader at the Biocenter of Julius-Maximilians-Universit\u00e4t W\u00fcrzburg (JMU), have played a leading role in this development. The results of their work have now been published in the latest issue of Nature Chemical Biology.<\/p>\n\n\n\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h3 class=\"wp-block-heading\">Making tumor-promoting proteins disappear<\/h3>\n\n\n\n<p>Cancers are usually triggered by tumorigenic proteins. Because cancer cells produce more of these proteins than normal cells, the dynamics are additionally increased. A common therapeutic approach is therefore to inhibit the function of these proteins with drugs. Although the proteins are then still there, they no longer function as well. This makes it possible to combat the tumor cells.<\/p>\n\n\n\n<p>However, the development of these inhibitors is difficult and has so far not been successful for all tumor-promoting proteins. To date, none of the candidates that inhibit Aurora has shown the desired results in clinical practice. The dream of many scientists is therefore to develop a drug that not only inhibits the tumor-promoting proteins but makes them disappear completely. A promising approach along this path could be a new class of substances with the scientific name \u201cPROTAC\u201d.<\/p>\n\n\n\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<h3 class=\"wp-block-heading\">In vitro cancer cells die<\/h3>\n\n\n\n<p>\u201cWe have developed such a PROTAC for Aurora,\u201d says Elmar Wolf. This PROTAC completely degrades the Aurora protein in cancer cells. Such cells cultivated in the laboratory died as a result. Wolf describes the mode of action of this substance as follows: \u201cThe tumor needs certain tumor-promoting proteins, which we can imagine as the pages of a book. Our PROTAC substance tears out the \u2018Aurora\u2019 pages and destroys them with the help of the machinery that every cell has to degrade old and broken proteins.\u201d PROTAC thus \u201cshreds\u201d the Aurora protein, as it were, until nothing of it remains.<\/p>\n\n\n\n<p>Professor Stefan Knapp from the Institute of Pharmaceutical Chemistry at Goethe University explains: \u201cAurora-A kinase is present in much higher concentrations in many cancer tissues than in healthy tissue and it also plays a key role in prostate cancer. Blocking the activity of Aurora-A kinase alone seems not a promising approach as none of the many clinically tested drug candidates has achieved clinical approval. With our PROTAC variant, we inhibit Aurora-A kinase via another, possibly more effective mechanism, which may open up new treatment options. That\u2019s why in the next step we\u2019ll test effectiveness and tolerance in animal models.\u201d<\/p>\n\n\n\n<div style=\"height:20px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"has-background has-very-light-gray-background-color\"><strong>Publication:<\/strong> PROTAC-mediated degradation reveals a non-catalytic function of AURORA-A kinase. Bikash Adhikari, Jelena Bozilovic, Mathias Diebold, Jessica Denise Schwarz, Julia Hofstetter, Martin Schr\u00f6der, Marek Wanior, Ashwin Narain, Markus Vogt, Nevenka Dudvarski Stankovic, Apoorva Baluapuri, Lars Sch\u00f6nemann, Lorenz Eing, Pranjali Bhandare, Bernhard Kuster, Andreas Schlosser, Stephanie Heinzlmeir, Christoph Sotriffer, Stefan Knapp and Elmar Wolf. Nature Chemical Biology, 28.09.2020. <a href=\"https:\/\/www.nature.com\/articles\/s41589-020-00652-y\" target=\"_blank\" rel=\"noreferrer noopener\" aria-label=\"https:\/\/www.nature.com\/articles\/s41589-020-00652-y (\u00f6ffnet in einem neuem Tab)\">https:\/\/www.nature.com\/articles\/s41589-020-00652-y<\/a><\/p>\n\n\n\n<p class=\"has-background has-very-light-gray-background-color\"><strong>PROTACS:<\/strong> <a href=\"https:\/\/aktuelles.uni-frankfurt.de\/englisch\/proxidrugs-project-led-by-goethe-university-included-in-clusters4future-programme\/\" target=\"_blank\" rel=\"noreferrer noopener\" aria-label=\"The cluster project PROXIDRUGS at Goethe University Frankfurt focuses on PROTACS (Proteolysis Targeting Chimeric Molecules). (\u00f6ffnet in einem neuem Tab)\">The cluster project PROXIDRUGS at Goethe University Frankfurt focuses on PROTACS (Proteolysis Targeting Chimeric Molecules).<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p>Researchers at Goethe University Frankfurt and the university of W\u00fcrzburg have developed a new compound for treating cancer. It destroys a protein that triggers its development. The villain in this [&hellip;]<\/p>\n","protected":false},"author":8,"featured_media":46389,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","_price":"","_stock":"","_tribe_ticket_header":"","_tribe_default_ticket_provider":"","_ticket_start_date":"","_ticket_end_date":"","_tribe_ticket_show_description":"","_tribe_ticket_show_not_going":false,"_tribe_ticket_use_global_stock":"","_tribe_ticket_global_stock_level":"","_global_stock_mode":"","_global_stock_cap":"","_tribe_rsvp_for_event":"","_tribe_ticket_going_count":"","_tribe_ticket_not_going_count":"","_tribe_tickets_list":"[]","_tribe_ticket_has_attendee_info_fields":false,"footnotes":""},"categories":[126,254],"tags":[243,244,245],"post_folder":[],"class_list":["post-46391","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-english","category-research","tag-biochemistry","tag-chemistry","tag-pharmacy"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>A cancer shredder: substance with new mechanism of action found | Aktuelles aus der Goethe-Universit\u00e4t Frankfurt<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/aktuelles.uni-frankfurt.de\/en\/english\/a-cancer-shredder-substance-with-new-mechanism-of-action-found\/\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A cancer shredder: substance with new mechanism of action found | Aktuelles aus der Goethe-Universit\u00e4t Frankfurt\" \/>\n<meta property=\"og:description\" content=\"Researchers at Goethe University Frankfurt and the university of W\u00fcrzburg have developed a new compound for treating cancer. 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