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NAMPT inhibition increases PD-L1 transcription via SIRT-mediated acetylation of NF-κB p65, and blocking PD-L1 elevates NAMPT through an HIF-1 dependent glycolysis pathway.",{"@graph":14,"@context":73},[15,34,56],{"@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/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-regulatory-relationship-between-nampt-and-pd-l1-in-cancer-and-identification-of-a-dual-targeting-inhibitor/333300/",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/the-regulatory-relationship-between-nampt-and-pd-l1-in-cancer-and-identification-of-a-dual-targeting-inhibitor/333300.png","ImageObject",300,407,{"name":42,"@type":43},"Olivia Brown","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is the reported relationship between NAMPT and PD-L1 in cancer cells?","Question",{"text":63,"@type":64},"The study reports a negative correlation between NAMPT expression and PD-L1 expression across various cancer cell lines.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does NAMPT inhibition affect PD-L1 expression?",{"text":68,"@type":64},"Pharmacological inhibition of NAMPT leads to transcriptional upregulation of PD-L1 through SIRT-mediated acetylation changes of NF-κB p65.",{"name":70,"@type":61,"acceptedAnswer":71},"What compound was designed to co-target NAMPT and PD-L1, and what effects were observed?",{"text":72,"@type":64},"A dual NAMPT/PD-L1 targeting compound, LZFPN-90, was designed and synthesized. It inhibits cell growth in a NAMPT-dependent manner, induces apoptosis, and under co-culture conditions enhances T-cell proliferation and activation while blocking cancer cell growth.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},333300,1790191069,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"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":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":112,"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":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":127,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144,"preview_page_count":4},16904993612988,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Article  \nThe regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor  \nYuan Yang1,2,6, Zefei Li3,6, Yidong Wang1,2, Jiwei Gao1,2, Yangyang Meng3, Simeng Wang 1,2, Xiaoyao Zhao1,2, Chengfang Tang1,2, Weiming Yang1,2, Yingjia Li1,2, Jie Bao4, Xinyu Fan5, Jing Tang 4, Jingyu Yang1,2, Chunfu Wu1,2, Mingze Qin 3 ✉ & Lihui Wang 1,2 ✉  \nAbstract  \nCancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted targetdependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PDL1 represents a promising therapeutic approach.  \nKeywords NAMPT/PD-L1; Co-targeting Therapy; Cancer; Tumor Immune Microenvironment  \nSubject Categories Cancer; Metabolism  \n[https://doi.org/10.1038/s44321-024-00051-z](https://doi.org/10.1038/s44321-024-00051-z)  \nReceived 23 August 2023; Revised 20 February 2024; Accepted 22 February 2024  \nPublished online: 6 March 2024  \nIntroduction  \nCancer is a complex and heterogeneous disease caused by multiple genetic changes and poses a major threat to human life (Siegel et al, 2023) . The cellular and structural heterogeneity of cancer determines the complexity of its metabolic patterns (Vitale et al, 2021) . Interestingly, these complex and diverse metabolic patterns also affect immune cells (Ghesquière et al, 2014; Mao et al, 2021) . Increasing evidence suggests that cancer metabolism not only plays a crucial role in sustaining the growth and survival of tumor cells but also contributes to the regulation of antitumor immune responses by regulating the release of metabolites and the expression of immune molecules (Leone et al, 2019; Xia et al, 2021) . However, the actual process underlying the interaction between cancer cell metabolism and immune response is not well understood.  \nNicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in redox reactions (Covarrubias et al, 2021) . Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis, is a key enzyme in cell metabolism that influences the activity of NAD+-dependent enzymes to regulate tumor metabolism (Gardell et al, 2019) . It has been reported that tumor cells consume NAD+ at a faster rate than normal cells, displaying very active metabolism, and expressing high levels of NAMPT to satisfy the high demand for NAD+ (Nakajima et al, 2009) . Several studies have shown that NAMPT and NAD+ are frequently upregulated in several human malignancies and play key roles in the development, progression, and recurrence of cancer (Lucena-Cacace et al, 2018; Zhang et al, 2019) . Furthermore, unlike tumor cells, which mostly depend on NAM","cbCaipelkOtxfI5S","https://ap.wps.com/l/cbCaipelkOtxfI5S","pdf",1958509,"English","# Introduction\n## Tumor metabolism and immune regulation\n## NAD+ metabolism and NAMPT in cancer\n## Checkpoint inhibitor immunotherapy and PD-L1","[{\"question\":\"What is the reported relationship between NAMPT and PD-L1 in cancer cells?\",\"answer\":\"The study reports a negative correlation between NAMPT expression and PD-L1 expression across various cancer cell lines.\"},{\"question\":\"How does NAMPT inhibition affect PD-L1 expression?\",\"answer\":\"Pharmacological inhibition of NAMPT leads to transcriptional upregulation of PD-L1 through SIRT-mediated acetylation changes of NF-κB p65.\"},{\"question\":\"What compound was designed to co-target NAMPT and PD-L1, and what effects were observed?\",\"answer\":\"A dual NAMPT/PD-L1 targeting compound, LZFPN-90, was designed and synthesized. It inhibits cell growth in a NAMPT-dependent manner, induces apoptosis, and under co-culture conditions enhances T-cell proliferation and activation while blocking cancer cell growth.\"}]","The regulatory relationship between NAMPT and PD-L1 in cancer and identification of a dual-targeting inhibitor | PDF",1790001834,48]