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A large-scale virtual screening of more than 12 million compounds identified N8 as a novel IKKε inhibitor based on docking score and drug-likeness. N8 inhibitory activity was validated in vitro across several cancer cell lines including HCT116, HepG2, T24, MDA-MB-231, A549, and HeLa, reducing viability, colony formation, and migration. In HCT116 colorectal cells, N8 showed superior efficacy versus established IKKε inhibitors. Mechanistically, N8’s anticancer effect appears driven by autophagy modulation rather than apoptosis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/discovery-of-n8-a-novel-ikk-inhibitor-with-potent-anticancer-activity-via-cytotoxicity-migration-suppression-and-autophagy-modulation/449342/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/discovery-of-n8-a-novel-ikk-inhibitor-with-potent-anticancer-activity-via-cytotoxicity-migration-suppression-and-autophagy-modulation/449342.png","ImageObject",300,407,{"name":92,"@type":93},"Blitz","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How was N8 identified as an IKKε inhibitor?","Question",{"text":112,"@type":113},"N8 was identified through large-scale virtual screening of over 12 million compounds and selected based on docking score and drug-likeness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which cancer cell lines were used to validate N8?",{"text":117,"@type":113},"Validation was performed in vitro across HCT116, HepG2, T24, MDA-MB-231, A549, and HeLa cell lines.",{"name":119,"@type":110,"acceptedAnswer":120},"Does N8 kill cancer cells mainly through apoptosis or autophagy?",{"text":121,"@type":113},"The anticancer activity is suggested to be mediated through modulation of autophagy rather than apoptosis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},449342,1791145102,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":81,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},24464137899374,"https://us-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","ReseaRch aRticle    \nDiscovery of N8: a novel IKKε inhibitor with potent anticancer activity via cytotoxicity, migration suppression, and autophagy modulation  \nWei Yea,b, siying Zhenga, hongmei Xiea, Xinrui Zhoua,b, Jiapeng Xua,b, Qiting luoa,b, Yuanyuan huanga, Jieyu lia, Jiayi Diaoa,b, Xinyi luoa,b, Qinchang Zhua and Ge liua  \nacollege of Pharmacy, shenzhen technology university, shenzhen, china; bschool of Pharmaceutical sciences, shenzhen university, shenzhen, china  \nABSTRACT  \nthe serine/threonine kinase iKKε is overexpressed or activated in various cancers, making it a promising therapeutic target. through a large-scale virtual screening of over 12 million compounds, we identified N8 as a novel iKKε inhibitor, selected for its favourable docking score and drug-likeness profile. the inhibitory activity of N8 on iKKε was validated in vitro across several cancer cell lines, including hct116 (colorectal), hepG2 (liver), t24 (bladder), MDa-MB-231 (breast), a549 (lung), and hela (cervical). N8 demonstrated significant reductions in cell viability, colony formation, and migration, particularly in hct116 colorectal cancer cells, where it exhibited superior efficacy compared to established iKKε inhibitors. Mechanistically, N8’s anticancer activity appears to be mediated through modulation of autophagy rather than apoptosis.  \nGRAPHICAL ABSTRACT  \nIntroduction  \nARTICLE HISTORY  \nReceived 1 May 2025 Revised 18 October 2025 accepted 16 December 2025  \nKEYWORDS  \ntargeted cancer therapy; iKKε; inhibitor; virtual screening; autophagy  \ncancer poses a serious threat to human health, and remains a leading cause of deaths worldwide1. Nearly 20 million new cancer cases and 9.7 million cancer-related deaths were reported in 2022 alone2. targeted drugs exhibit higher efficacy and specificity and lower toxicity against a variety of malignant tumours than conventional cancer treatment modes such as chemotherapy; as such, they have become the mainstay of cancer therapy over the last decade3. Kinases play significant regulatory roles in the formation and progression of numerous tumours and have been successfully targeted to treat cancer4. the first small-molecule protein kinase inhibitor, imatinib, was approved for use in patients with cancer by the United states Food  \nCONTACT Ge liu  [liuge@sztu.edu.cn](liuge@sztu.edu.cn); Qinchang zhu  zhuqc@szu.edu.cn  college of Pharmacy, shenzhen technology university, 3002 lantian road, Pingshan district, shenzhen, 518118, china  \n supplemental data for this article can be accessed online at [https://doi.org/10.1080/14756366.2025.2607808](https://doi.org/10.1080/14756366.2025.2607808) .  \n© 2025 the author(s) . Published by Informa uK limited, trading as taylor & francis Group  \nthis is an open access article distributed under the terms of the creative commons attribution-noncommercial license ([http://creativecommons.org/licenses/](http://creativecommons.org/licenses/)[ ](http://creativecommons.org/licenses/)[by-nc/4.0/](by-nc/4.0/)), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. the termson which this article has been published allow the posting of the accepted manuscript in a repository by the author(s) or with their consent.  \n2  W. Ye et al.  \nand Drug administration (FDa) in 20015. since then, 71 small-molecule kinase inhibitors have been approved by the FDa6. Over the last 5 years, the FDa has approved 37 small-molecule kinase inhibitors, which accounts for approximately 15% of all new drugs approved by the FDa, demonstrating the promising potential of these therapeutic agents7. Despite these advances in the discovery of small-molecule kinase inhibitors, few have proved effective in treating tumour metastasis owing to toxicity and drug resistance. thus, there is an urgent need for a new generation of safe but effective targeted therapeutic agents.  \ninhibitor of nuclear factor kappa B kinase ε (iKKε) is","cbCaiiDIMDUuW0vy","https://ap.wps.com/l/cbCaiiDIMDUuW0vy","pdf",2565764,15,"English","# Introduction\n# Article information\n## Received/Accepted dates\n# Keywords\n# Methods and results overview\n## Virtual screening and compound selection\n## In vitro validation across cancer cell lines\n## Effects on viability, colony formation, migration\n## Mechanistic interpretation via autophagy","[{\"question\":\"How was N8 identified as an IKKε inhibitor?\",\"answer\":\"N8 was identified through large-scale virtual screening of over 12 million compounds and selected based on docking score and drug-likeness.\"},{\"question\":\"Which cancer cell lines were used to validate N8?\",\"answer\":\"Validation was performed in vitro across HCT116, HepG2, T24, MDA-MB-231, A549, and HeLa cell lines.\"},{\"question\":\"Does N8 kill cancer cells mainly through apoptosis or autophagy?\",\"answer\":\"The anticancer activity is suggested to be mediated through modulation of autophagy rather than apoptosis.\"}]","Discovery of N8 - a novel IKKε inhibitor with potent anticancer activity via cytotoxicity, migration suppression, and autophagy modulation | PDF",1790729966,38]