{"id":17051,"date":"2022-04-28T09:07:04","date_gmt":"2022-04-28T09:07:04","guid":{"rendered":"https:\/\/www.sygnaturediscovery.com\/blog\/5-things-you-should-know-about-protacs\/"},"modified":"2022-04-28T09:07:04","modified_gmt":"2022-04-28T09:07:04","slug":"5-things-you-should-know-about-protacs","status":"publish","type":"blog","link":"https:\/\/www.sygnaturediscovery.com\/fr\/blog\/5-things-you-should-know-about-protacs\/","title":{"rendered":"5 things you should know about PROTACs"},"content":{"rendered":"<p><span style=\"font-size: 14pt;\"><strong><a href=\"https:\/\/www.sygnaturediscovery.com\/drug-discovery\/integrated-drug-discovery\/targeted-protein-degradation\/protac-protein-degraders\/\">PROTAC\u00ae protein degraders<\/a> (or proteolysis targeting chimeras, to get all formal) are a hot topic at the moment. <\/strong><\/span><span style=\"font-size: 14pt;\"><strong>If you work in drug discovery, chances are you\u2019ve heard all about PROTACs and their potential to revolutionise the industry. <\/strong><\/span><span style=\"font-size: 14pt;\"><strong>They take advantage of the body\u2019s natural waste disposal system by encouraging the ubiquitin proteasome system to mark a target protein for degradation \u2013 providing scientists with an intriguing alternative to a small molecule inhibitor or antibody. <\/strong><\/span><span style=\"font-size: 14pt;\"><strong>But aside from the basics and the buzz, what else do you need to know about PROTACs?<\/strong><\/span><\/p>\n<div style=\"width: 1444px;\" class=\"wp-video\"><video class=\"wp-video-shortcode\" id=\"video-17051-1\" width=\"1444\" height=\"1012\" loop autoplay preload=\"auto\" controls=\"controls\"><source type=\"video\/mp4\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2022\/03\/PROTAC_video.mp4?_=1\"><\/source><a href=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2022\/03\/PROTAC_video.mp4\">https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2022\/03\/PROTAC_video.mp4<\/a><\/video><\/div>\n<p><span style=\"font-size: 10pt;\"><em>A video depiction of dBET6, a PROTAC\u00ae targeted degrader, bound in the CRBN-BRD4 complex (6boy.pdb)<\/em><\/span><\/p>\n<p>\u00a0<\/p>\n<h2><strong>1. Pharma is betting big on them<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">Money is pouring into this exciting and potentially incredibly fruitful field.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">In fact, a report published last year <a href=\"https:\/\/www.rootsanalysis.com\/press-releases\/234-the-targeted-protein-degradation-enabling-technologies-market-featuring-a-healthy-pipeline-of-novel-therapeutics-is-anticipated-to-be-worth-over-usd-33-billion-by-2030-predicts-roots-analysis.html\" target=\"_blank\" rel=\"noopener\">claimed<\/a> that over $5bn had been invested into companies or projects involved in target protein degraders since 2014, with around 26% of these pipeline drugs being PROTACs.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The same report predicts that the compound annual growth rate of the <a href=\"https:\/\/www.sygnaturediscovery.com\/drug-discovery\/integrated-drug-discovery\/targeted-protein-degradation\/\">targeted protein degradation<\/a> market will be around 27% until 2030 \u2013 suggesting that the popularity of PROTACs is here to stay.<\/span><\/p>\n<p>\u00a0<\/p>\n<h2><strong>2. They\u2019re not <em>that <\/em>new\u2026<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">PROTACs may have only reached the mainstream recently, but the idea behind them goes back further than you might think.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">In fact, the concept originated in the late 1990s, and was <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC37474\/\" target=\"_blank\" rel=\"noopener\">first written about<\/a> in Proceedings of the National Academy of Sciences of the United States of America as long ago as July 2001.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The big breakthrough, so to speak, occurred in 2015, when non-peptidic VHL binders <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acschembio.5b00216\" target=\"_blank\" rel=\"noopener\">were used<\/a> as ligands for the E3 enzyme.<\/span><\/p>\n<p>\u00a0<\/p>\n<h2><strong>3. They\u2019re no one-hit wonder<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">PROTACs can be recycled and used for subsequent rounds of degradation.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">The PROTAC\u00ae molecule disassociates from the ubiquitin ligase complex once the target protein has been dispatched to the proteasome, before then attaching itself to a new target and E3 ligase to initiate another catalytic cycle.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">In this way, just one single degrader molecule can remove many molecules of a target protein \u2013 meaning PROTACs may be potent at relatively low concentrations, therefore potentially reducing the incidence of off-target effects.<\/span><\/p>\n<p>\u00a0<\/p>\n<div id=\"attachment_12563\" style=\"width: 910px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" aria-describedby=\"caption-attachment-12563\" class=\"wp-image-12563\" src=\"https:\/\/www.sygnaturediscovery.com\/wp-content\/uploads\/2025\/11\/6boy_2800-featured3.png\" alt='6boy: Crystal structure of a \"PROTAC\" targeted degrader complex: DDB1-CRBN-BRD4 complex bound to dBET6 PROTAC' width=\"900\" height=\"361\"><p id=\"caption-attachment-12563\" class=\"wp-caption-text\">A depiction of dBET6, a PROTAC\u00ae targeted degrader, bound in the CRBN-BRD4 complex (6boy.pdb)<\/p><\/div>\n<p>\u00a0<\/p>\n<h2><strong>4. They were considered to fight COVID-19<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">We\u2019ve seen the successes of widespread vaccination, and several antibody and antiviral treatments have recently been approved for use to protect the pandemic\u2019s more vulnerable patients.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">But back in September 2020, an <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7462587\/\" target=\"_blank\" rel=\"noopener\">article<\/a> in Drug Discovery Today proposed PROTACs as a potential method of treating or preventing COVID-19, concluding that \u00ab\u00a0in principle, oral antiviral PROTACs could be used prophylactically to prevent viral infection in addition to therapeutically to promote protein degradation and host immune response in the case of confirmed disease\u00a0\u00bb.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">There appears to be uptake of this idea in the industry, with Nurix Therapeutics having <a href=\"https:\/\/www.nature.com\/articles\/s41573-021-00371-6\" target=\"_blank\" rel=\"noopener\">announced<\/a> efforts to generate PROTACs for treatment of COVID-19.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">Evidence, perhaps, of the novelty and untapped potential of this class of drug.<\/span><\/p>\n<p>\u00a0<\/p>\n<h2><strong>5. They\u2019re in the clinic<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">We\u2019re already seeing PROTACs progress through drug discovery pipelines with promising success.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">A targeted protein degrader first reached the clinic <a href=\"https:\/\/www.nature.com\/articles\/d41573-019-00043-6\" target=\"_blank\" rel=\"noopener\">in 2019<\/a>. Soon, many more followed.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">By March 2021, in fact, a <a href=\"https:\/\/www.nature.com\/articles\/d41573-021-00052-4\" target=\"_blank\" rel=\"noopener\">Nature article<\/a> claimed that no fewer than 15 deliberately designed degraders were expected to be in clinical trials later that year.<\/span><\/p>\n<p><span style=\"font-size: 14pt;\">With investment continuing and more PROTAC\u00ae projects taking shape, that number is likely to grow significantly in the years ahead.<\/span><\/p>\n<p>\u00a0<\/p>\n<h2><strong>Want to discuss PROTACs?<\/strong><\/h2>\n<p><span style=\"font-size: 14pt;\">Designing a <a href=\"https:\/\/www.sygnaturediscovery.com\/drug-discovery\/integrated-drug-discovery\/targeted-protein-degradation\/protac-protein-degraders\/\">PROTAC\u00ae<\/a> from scratch can present complex challenges. Luckily, our scientists are here to help \u2013 get in touch with us via the form below or our <a href=\"https:\/\/www.sygnaturediscovery.com\/fr\/contact\/\">contact page<\/a>.<\/span><\/p>\n<p>\u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Explore Sygnature Discovery&rsquo;s comprehensive solutions in drug discovery as we delve into the world of PROTAC\u00ae targeted protein degraders.<\/p>\n","protected":false},"featured_media":17053,"template":"","category":[29],"class_list":["post-17051","blog","type-blog","status-publish","has-post-thumbnail","hentry","category-non-categorise"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.5 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>5 things you should know about PROTACs - Sygnature<\/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:\/\/www.sygnaturediscovery.com\/fr\/blog\/5-things-you-should-know-about-protacs\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"5 things you should know about PROTACs - 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