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From Screening to Success: How Molecular 'Super-Glue' SJ3149, Could Advance Cancer Treatments
<!doctype html><html lang="en"><head> <meta charset="utf-8"> <title>From Screening to Success: How Molecular 'Super-Glue' SJ3149, Could Advance Cancer Treatments </title> <link rel="shortcut icon" href="https://oxfordglobal.com/hubfs/OXFORD_GLOBAL-LOGO_SYMBOL.jpg"> <meta name="description" content="Researchers at St Jude Children's Research Hospital used high throughput screening (HTS) to identify SJ3149, a molecular glue degrader. This small molecule demonstrated efficacy across a range of cancer types."> <meta name="viewport" content="width=device-width, initial-scale=1"> <meta property="og:description" content="Researchers at St Jude Children's Research Hospital used high throughput screening (HTS) to identify SJ3149, a molecular glue degrader. 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This small molecule demonstrated efficacy across a range of cancer types. </div> </div> <div class="header-graphic flex-1"> <img src="https://oxfordglobal.com/hubfs/Website/Images/Resources/Discovery/From%20Screening%20to%20Success%20How%20Molecular%20Super-Glue%20SJ3149%2c%20Could%20Advance%20Cancer%20Treatments.png" class="header-graphic-image"> </div> </div> </div> </div> <div class="container-wrapper"> <div class="wide-container"> <div class="content"> <div class="content-body text-gap"> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"><strong>HTS in Drug Discovery</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">Developing new drugs requires considering a very large number of molecules in the molecular space and identifying suitable candidates that can be investigated in more depth for their use as potential therapeutics. HTS plays a crucial role in this process; it <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/high-throughput-screening#:~:text=6%20High%2DThroughput%20Screening,hundreds%20of%20thousands%20of%20times" rel="noopener" target="_blank"><span style="color: #4a6ee0;">enables a biochemical or cellular event to be reproducibly and rapidly tested against chemical entities</span></a>. </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">Furthermore, HTS can run millions of chemical tests in a short time, making drug discovery processes more efficient. The results from the HTS provide a foundation upon which drug design is used to generate lead compounds with physicochemical properties for therapeutic uses.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"><strong>Case Study: Application of Molecular Glues in Cancer Therapeutics</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">Molecular glues manipulate a cell's inherent protein recycling mechanism by inducing a specific interaction between an E3 ligase and a target protein, resulting in proteasomal degradation. Given the challenge of effectively targeting cancer-related proteins with conventional small molecule inhibitors, molecular glues present a promising therapeutic alternative.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">A group of scientists at St Jude Children's Research Hospital joined forces <a href="https://www.nature.com/articles/s41467-024-44698-1" rel="noopener" target="_blank"><span style="color: #4a6ee0;">to improve an existing chemical compound (SJ7095) to develop a new molecular glue degrader, SJ3149</span></a>. SJ3149 was hailed a molecular 'super-glue,' due to its impressive antiproliferative activity against a range of human cancer cell lines.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">SJ3149 <a href="https://www.stjude.org/media-resources/news-releases/2024-medicine-science-news/molecular-super-glue-shows-promise-of-cancer-drug-discovery-platform.html" rel="noopener" target="_blank"><span style="color: #4a6ee0;">binds to the cancer-related protein casein kinase 1 alpha (CK1α), leading to its degradation and subsequent destruction</span></a>. Zoran Rankovic, Director at St Jude Children's Research Hospital reiterated the novel and impressive nature of SJ3149 by stating: "SJ3149 is the first-in-class potent and selective CK1α degrader, showing efficacy in both in vitro and in vivo cancer models."</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"><strong>Related: </strong></p> <ul> <li style="text-align: justify;"><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/interview-with-felix-hausch-professor-for-structure-based-drug-research-at-tu-darmstadt" rel="noopener" target="_blank"><span style="color: #4a6ee0;">Interview with Felix Hausch, Professor for Structure Based Drug Research at TU Darmstadt</span></a></span> </li> <li style="text-align: justify;"><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/spheroids-assembloids-could-unlock-high-throughput-screening-of-neuro-drugs" rel="noopener" target="_blank"><span style="color: #4a6ee0;">Spheroids, Assembloids Could Unlock High Throughput Screening of Neuro Drugs</span></a></span></li> <li style="text-align: justify;"><span style="color: windowtext;"><a href="https://oxfordglobal.com/discovery/resources/challenges-and-opportunities-in-targeted-protein-degradation-current-and-future-strategies" rel="noopener" target="_blank"><span style="color: #4a6ee0;">Challenges and Opportunities in Targeted Protein Degradation: Current and Future Strategies</span></a></span> </li> </ul> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">The lead scientists at St. Jude Children's Research Hospital <a href="https://cbirt.net/the-glue-that-heals-st-judes-researchers-unveil-molecular-super-glue-propelling-innovative-cancer-drug-development/#google_vignette" rel="noopener" target="_blank"><span style="color: #4a6ee0;">developed a large proprietary library of 3630 compound molecular glues</span></a>. This library underwent HTS against nine paediatric cancer cell lines using 384-well plates to assess their activity across various cancer types. Through clustering analysis, compounds with distinct activity profiles were identified. The HTS process led to the identification of an initial hit.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">Following hit optimisation, SJ3149 exhibited increased potency and fewer off-target effects compared to similar compounds. SJ3149 also shared a similar profile to a class of approved cancer drugs, further indicating its credibility and clinical usefulness. The outcome of this study showed that SJ3149 effectively destroyed CK1α in cancer cells, resulting in reduced tumour growth.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"><strong>Conclusion</strong></p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">This experiment points to the potential of molecular glue degraders in targeting specific proteins for degradation, offering a unique approach to cancer treatment. Furthermore, SJ3149 displayed compatibility with existing treatments, highlighting its patient-friendly nature and potential applicability to a wider population of cancer patients.</p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;"> </p> <p style="margin-top: 0cm; margin-right: 0cm; margin-bottom: 0cm; text-align: justify; padding-left: 0cm;">Overall, these findings represent a significant advancement in tailored medicine development, with molecular glues playing a pivotal role in the emerging field of chemical biology. Furthermore, the study shows that HTS plays a crucial part in identifying and optimising hits.</p> <p style="text-align: justify;"> </p> <div class="content-body-footer"> </div> </div> <div class="content-sidebar"> <div class="related-articles"> <h3 class="center">Related Resources</h3> <div class="article"> <a href="/discovery-development/resources/alzheimers-brain-awareness-month-spotlight-how-amphista-therapeutics-is-tackling-neurological-disorders"> <div class="cover-graphic"> <img src="https://oxfordglobal.com/hubfs/Website/Images/Resources/Discovery/Brain%20Awareness%20Month.jpg" class="cover-graphic-image"> </div> </a><div class="content"><a href="/discovery-development/resources/alzheimers-brain-awareness-month-spotlight-how-amphista-therapeutics-is-tackling-neurological-disorders"> <h4> Alzheimer's & Brain Awareness Month Spotlight: How Amphista Therapeutics is Tackling Neurological Disorders </h4> <div class="abstract"> To honour Alzheimer's & Brain Awareness Month, this article will acknowledge Amphista Therapeutics' use of targeted protein degradation (TPD) to treat symptoms of neurological disorders. </div> <div class="read-more"> <a href="/discovery-development/resources/alzheimers-brain-awareness-month-spotlight-how-amphista-therapeutics-is-tackling-neurological-disorders" class="read-more-link">Read More</a> </div></a> </div> </div> <div class="article"> <a href="/discovery-development/resources/new-class-of-molecular-glues-could-reshape-cancer-drug-discovery"> <div class="cover-graphic"> <img src="https://oxfordglobal.com/hubfs/Website/Images/Resources/Discovery/New%20Class%20of%20Molecular%20Glues%20Could%20Transform%20Cancer%20Drug%20Discovery.jpg" class="cover-graphic-image"> </div> </a><div class="content"><a href="/discovery-development/resources/new-class-of-molecular-glues-could-reshape-cancer-drug-discovery"> <h4> New Class of Molecular Glues Could Reshape Cancer Drug Discovery </h4> <div class="abstract"> A research group at the University of Dundee discovered new molecular glues, expanding the targeted protein degradation field. </div> <div class="read-more"> <a href="/discovery-development/resources/new-class-of-molecular-glues-could-reshape-cancer-drug-discovery" class="read-more-link">Read More</a> </div></a> </div> </div> </div> </div> </div> </div> </div> </div> <div class="newsletter-cta"> <h2 class="heading">Subscribe to our newsletter</h2> <div class="message"> Sign up for our monthly Newsletter to keep up with all things Discovery & Development </div> <div class="button-wrapper"> <a href="#" class="button hs-cta-trigger-button hs-cta-trigger-button-177049184347">Newsletter Sign-Up</a> </div> </div> </main> <div data-global-resource-path="git/og-stage/templates/partials/footer.html"><footer class="website-footer flex flex-column g-20"> <div class="footer-columns"> <div class="footer-column"> <a href="https://oxfordglobal.com" class="site-logo-link"> <img src="https://oxfordglobal.com/wp-content/uploads/2023/03/Oxford-Global-Logo-Stacked-Websize.png" class="site-logo"> </a> </div> <div class="footer-column"> <h3>Brands</h3> <ul> <li> <a href="/precision-medicine/">Precision Medicine</a> </li> <li> <a href="/discovery-development/">Discovery & Development</a> </li> <li> <a href="/nextgen-biomed/">NextGen Biomed</a> </li> </ul> </div> <div class="footer-column"> <h3>Services</h3> <ul> <li> <a href="https://oxfordglobal.com/in-person-services/"> In-Person Services </a> </li> <li> <a href="https://oxfordglobal.com/digital-marketing-services/"> Digital Marketing Services </a> </li> </ul> <h3>Upcoming Events</h3> <ul> <li> <a href="https://oxfordglobal.com/calendar/"> Event Calendar </a> </li> </ul> </div> <div class="footer-column"> <h3>Company</h3> <ul> <li class="elementor-icon-list-item"> <a href="https://oxfordglobal.com/about-us/"> About </a> </li> <li class="elementor-icon-list-item"> <a href="https://oxfordglobal.com/vacancies/"> Vacancies </a> </li> <li class="elementor-icon-list-item"> <a href="https://oxfordglobal.com/csr-policy/"> CSR Policy </a> </li> <li class="elementor-icon-list-item"> <a href="javascript:postMessage({type:'HS_DISPLAY_CALL_TO_ACTION',id:130207947529});"> Contact </a> </li> </ul> </div> <div class="footer-column"> <p> <a href="tel:+441865248455">+44 1865 248 455</a><br> <a href="mailto:help@oxfordglobal.com">help@oxfordglobal.com</a> </p> <p> <strong>Our UK Address:</strong><br> Godstow Court<br> Minns Business Park<br> Botley<br> Oxford, OX2 0JB </p> <p> <strong>Our US Address:</strong><br> 100 Cambridge Street<br> 14th Floor<br> Boston<br> MA 02114 </p> </div> </div> <div class="footer-bottom grid g-20"> <div class="span8 span12-sm span12-md flex flex-column g-10"> <div class="copyright"> © Oxford Global Marketing Ltd. 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