{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:54:56Z","timestamp":1781585696669,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2023GXNSFBA026079"],"award-info":[{"award-number":["2023GXNSFBA026079"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82404696"],"award-info":[{"award-number":["82404696"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017691","name":"Guangxi Key Research and Development Program","doi-asserted-by":"publisher","award":["Guike AB25069036"],"award-info":[{"award-number":["Guike AB25069036"]}],"id":[{"id":"10.13039\/501100017691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Non\u2010small cell lung cancer (\n NSCLC<\/jats:styled-content>\n ) is the leading cause of cancer\u2010related death worldwide. Cyclin\u2010dependent kinase 4 (\n CDK4<\/jats:styled-content>\n ) is a well\u2010validated oncogenic driver in\n NSCLC<\/jats:styled-content>\n , yet current\n CDK4<\/jats:styled-content>\n inhibitors\u2014predominantly based on the aminopyrimidine scaffold\u2014are limited by structural homogeneity and the rapid emergence of acquired resistance, underscoring the need for novel chemotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We employed a\n HuProt<\/jats:styled-content>\n human proteome microarray to screen for direct cellular targets of artesunate, an\n FDA<\/jats:styled-content>\n \u2010approved artemisinin derivative. Candidate interactions were validated by molecular docking, surface plasmon resonance (\n SPR<\/jats:styled-content>\n ), and in\u00a0vitro kinase assays. Functional effects were assessed in\n A549<\/jats:styled-content>\n and\n H1299 NSCLC<\/jats:styled-content>\n cell lines using flow cytometry and Western blotting.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Artesunate was identified as a direct binder of\n CDK4<\/jats:styled-content>\n , with molecular docking revealing a strong binding affinity (\u22127.069\u2009kcal\/mol).\n SPR<\/jats:styled-content>\n analysis confirmed this interaction with a\n K<\/jats:italic>\n \n d<\/jats:italic>\n <\/jats:sub>\n of 488\u2009\n \u03bcM<\/jats:styled-content>\n , and in\u00a0vitro kinase assays demonstrated potent inhibition of\n CDK4<\/jats:styled-content>\n \/Cyclin\n D3<\/jats:styled-content>\n activity (\n \n IC\n 50<\/jats:sub>\n <\/jats:styled-content>\n \u2009=\u20090.2943\u2009\n \u03bcM<\/jats:styled-content>\n ). Treatment with artesunate induced significant\n G0<\/jats:styled-content>\n \/\n G1<\/jats:styled-content>\n cell cycle arrest in both\n A549<\/jats:styled-content>\n and\n H1299<\/jats:styled-content>\n cells. This effect was mediated through inhibition of the\n CDK4<\/jats:styled-content>\n \u2013Rb\u2013\n E2F<\/jats:styled-content>\n axis, as evidenced by dose\u2010dependent suppression of Rb phosphorylation at Ser780 and Ser795.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our findings establish artesunate as a structurally distinct, non\u2010aminopyrimidine\n CDK4<\/jats:styled-content>\n inhibitor with potent biochemical and cellular activity in\n NSCLC<\/jats:styled-content>\n models. This work provides a promising therapeutic strategy to circumvent resistance associated with current\n CDK4<\/jats:styled-content>\n inhibitors and supports the repurposing of artesunate for\n CDK4<\/jats:styled-content>\n \u2010driven cancers.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.71907","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T05:03:15Z","timestamp":1777957395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Artesunate Induces\n G0<\/scp>\n \/\n G1<\/scp>\n Phase Arrest in Tumor Cells and Associates With Cyclin\u2010Dependent Kinase 4 (\n CDK4<\/scp>\n )"],"prefix":"10.1002","volume":"15","author":[{"given":"Xinyu","family":"Chi","sequence":"first","affiliation":[{"name":"Research Center of Communicable and Severe Diseases The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qicong","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Oncology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Oncology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Oncology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenhong","family":"Qu","sequence":"additional","affiliation":[{"name":"Institute of Oncology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosu","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Oncology The People's Hospital of Guangxi Zhuang Autonomous Region Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202400666"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201059623\u20103"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0145\u20102023"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2024.101103"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010000847"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.10"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113754"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2023.106705"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107526"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2022.03.051"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157085"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002305\u20109"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107733"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202502617"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.106046"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102164\u201013\u2010633"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20103803"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.05.353"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102023\u2010007126"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.10.013"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010025\u201001395\u20103"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2025.115622"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201047606\u20109"}],"container-title":["Cancer 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