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Using chemical biology target deconvolution and downstream transcriptomic, functional, and genetic rescue analyses, the work links TSN action to DDX5 degradation and suppression of the pro-survival c-Myc axis.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/toosendanin-suppresses-acute-myeloid-leukemia-by-targeting-ddx5c-myc-axis-to-inhibit-protein-synthesis/360860/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/toosendanin-suppresses-acute-myeloid-leukemia-by-targeting-ddx5c-myc-axis-to-inhibit-protein-synthesis/360860.png","ImageObject",300,407,{"name":42,"@type":43},"Blitz","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What problem in acute myeloid leukemia motivates this study?","Question",{"text":62,"@type":63},"AML continues to face poor long-term outcomes because relapse and drug resistance limit the effectiveness of existing therapies.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How was the molecular target of toosendanin in AML identified?",{"text":67,"@type":63},"An integrated chemical biology workflow was used, including affinity pull-down, CETSA, DARTS, and molecular docking, followed by transcriptomic and genetic rescue experiments.",{"name":69,"@type":60,"acceptedAnswer":70},"What is the proposed mechanism linking toosendanin to reduced leukemia progression?",{"text":71,"@type":63},"TSN directly targets the RNA helicase DDX5, promoting its degradation and thereby impairing the c-Myc transcriptional network, which suppresses ribosome biogenesis and global protein synthesis.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},360860,1790867454,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":33,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},24464137899374,"https://us-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","He etal. Journal of Translational Medicine (2026) 24:862  \n[https://doi.org/10.1186/s12967-026-08339-z](https://doi.org/10.1186/s12967-026-08339-z)  \nJournal of Translational Medicine  \nRESEARCH Open Access  \nToosendanin suppresses acute myeloid leukemia by targeting DDX5/c-Myc axis to inhibit protein synthesis  \nXianchao He1†, Zhiwei Chen3†, Jing Luo4, Hongru Chen5, Yu Hou2, Dan Liu6* and Yuanyuan Liu2*  \nAbstract  \nBackground Acute myeloid leukemia (AML) remains a therapeutic challenge due to relapse and resistance, driving the need for novel therapeutic strategies. While the natural compound toosendanin (TSN) has shown anti-tumor activity in solid cancers, its mechanism of action and direct molecular targets in AML are unknown.  \nMethods We utilized an integrated chemical biology approach (affinity pull-down, cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) assay, molecular docking) for target deconvolution. Downstream mechanisms were dissected using transcriptomic (RNA-seq), functional assays and genetic rescue experiments. Efficacy and toxicity were evaluated in an MLL-AF9-driven AML mouse model.  \nResults TSN exhibited potent anti-AML activity at nanomolar concentrations, inhibiting cell proliferation, inducing dual G0/G1 and G2/M phase arrest, and triggering caspase-dependent apoptosis. To uncover the mechanism, we identified the RNA helicase DDX5 as a novel, direct cellular target of TSN. TSN binding promoted DDX5 degradation via both proteasomal and lysosomal pathways, a dual mechanism ensuring its efficient depletion. Subsequent transcriptomic analyses revealed that TSN, via targeting DDX5, impaired the oncogenic c-Myc transcriptional network, leading to suppressed ribosome biogenesis and global protein synthesis. Genetic rescue experiments linked DDX5 to these effects. Importantly, in preclinical AML model, TSN treatment significantly prolonged survival without observable toxicity, confirming its therapeutic potential.  \nConclusions Our study delineates a coherent and novel anti-leukemic pathway: TSN suppresses AML by directly targeting DDX5 for degradation, thereby inhibiting the pro-survival c-Myc axis. These findings elucidate the pharmacology of TSN and validate the DDX5/c-Myc axis as a promising therapeutic candidate in AML.  \nKeywords Toosendanin, Acute myeloid leukemia, DDX5, c-Myc, Ribosome biogenesis  \n†Xianchao He and Zhiwei Chen contributed equally to this work.  \n*Correspondence:  \nDan Liu [jackieliu10@126.com](jackieliu10@126.com)[ ](jackieliu10@126.com)Yuanyuan Liu [Liuyuanyuan@cqmu.edu.cn](Liuyuanyuan@cqmu.edu.cn)  \n1Guizhou University Medical College, Guiyang 550025, Guizhou Province, China  \n2Department of Radiological Medicine, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China  \n3School of Traditional Chinese Medicine, Chongqing University of Chinese Medicine, Chongqing 402760, China  \n4Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China  \n5The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China  \n6Department of Radiology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402160, China  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not includ","cbCaibbY12Op2KLq","https://ap.wps.com/l/cbCaibbY12Op2KLq","pdf",13247923,18,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Clinical challenge in AML\n## Natural products and TSN","[{\"question\":\"What problem in acute myeloid leukemia motivates this study?\",\"answer\":\"AML continues to face poor long-term outcomes because relapse and drug resistance limit the effectiveness of existing therapies.\"},{\"question\":\"How was the molecular target of toosendanin in AML identified?\",\"answer\":\"An integrated chemical biology workflow was used, including affinity pull-down, CETSA, DARTS, and molecular docking, followed by transcriptomic and genetic rescue experiments.\"},{\"question\":\"What is the proposed mechanism linking toosendanin to reduced leukemia progression?\",\"answer\":\"TSN directly targets the RNA helicase DDX5, promoting its degradation and thereby impairing the c-Myc transcriptional network, which suppresses ribosome biogenesis and global protein synthesis.\"}]","Toosendanin suppresses acute myeloid leukemia by targeting DDX5/c-Myc axis to inhibit protein synthesis | PDF",1790141845,45]