{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:23:08Z","timestamp":1787844188184,"version":"build-2784847793"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3400500"],"award-info":[{"award-number":["2022YFC3400500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473893"],"award-info":[{"award-number":["82473893"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20108"],"award-info":[{"award-number":["U23A20108"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304301"],"award-info":[{"award-number":["82304301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22377013"],"award-info":[{"award-number":["22377013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M783613"],"award-info":[{"award-number":["2025M783613"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24JS2830200"],"award-info":[{"award-number":["24JS2830200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["YDZX20233100004032"],"award-info":[{"award-number":["YDZX20233100004032"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The classical sequential workflow\u2014individual compound screening, followed by stepwise design\u2010synthesis\u2010purification of derivatives\u2014makes lead compound discovery time\u2010consuming and cost\u2010prohibitive. Herein, we developed Affinity Selection Thin\u2010Layer Chromatography (AS\u2010TLC) as a method for high\u2010throughput screening (HTS), enabling efficient and cost\u2010effective screening of compound mixtures. Furthermore, we integrated activity assays with AS\u2010TLC to minimize target protein consumption and lower the false positive rate, through which we identified a YTH domain\u2010containing protein 1 (YTHDC1) inhibitor, fragment YD, with a half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) of 20.01\u00a0\u00b1\u00a03.30\u00a0\u00b5\n                    <jats:sc>m<\/jats:sc>\n                    . Building on this hit, we applied copper(I)\u2010catalyzed azide\u2013alkyne cycloaddition (CuAAC)\u00a0click chemistry for rapid structural modification and compound library construction, ultimately obtaining LC\u2010YD03 with significantly enhanced inhibitory activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a041.98\u00a0\u00b1\u00a06.24\u00a0n\n                    <jats:sc>m<\/jats:sc>\n                    ). The interaction mode between LC\u2010YD03 and YTHDC1 was further clarified via X\u2010ray crystallographic analysis. This study demonstrates that the AS\u2010TLC\u2010activity assay platform enables efficient hit screening from compound mixtures; subsequent click chemistry\u2010based combinatorial library technology accelerates lead compound optimization. Collectively, this workflow significantly reduces the time and cost associated with lead compound discovery.\n                  <\/jats:p>","DOI":"10.1002\/advs.77386","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:13:42Z","timestamp":1787843622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AS\u2010TLC\u2010Based High\u2010Throughput Screening Integrated with CuAAC Optimization Strategy Facilitates the Rapid Discovery of YTHDC1 Inhibitor"],"prefix":"10.1002","author":[{"given":"Mingchen","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Precision Medicine Research Institute of Guizhou and Guizhou Provincial Key Laboratory of Digestive System Diseases The Affiliated Hospital of Guizhou Medical University Guizhou Medical University  Guiyang China"},{"name":"Innovation Center for AI and Drug Discovery School of Pharmacy East China Normal University  Shanghai China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiping","family":"Fu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Gao","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwei","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Innovation Center for AI and Drug Discovery School of Pharmacy East China Normal University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hesong","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University the Key Laboratory of Innate Immune Biology of Fujian Province Biomedical Research Center of South China College of Life Sciences Fujian Normal University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Innovation Center for AI and Drug Discovery School of Pharmacy East China Normal University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University the Key Laboratory of Innate Immune Biology of Fujian Province Biomedical Research Center of South China College of Life Sciences Fujian Normal University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1529-6329","authenticated-orcid":false,"given":"Chujiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Precision Medicine Research Institute of Guizhou and Guizhou Provincial Key Laboratory of Digestive System Diseases The Affiliated Hospital of Guizhou Medical University Guizhou Medical University  Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixian","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8920-9355","authenticated-orcid":false,"given":"Huan","family":"Xiong","sequence":"additional","affiliation":[{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3864-8382","authenticated-orcid":false,"given":"Cheng","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Precision Medicine Research Institute of Guizhou and Guizhou Provincial Key Laboratory of Digestive System Diseases The Affiliated Hospital of Guizhou Medical University Guizhou Medical University  Guiyang China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"},{"name":"Zhongshan Institute for Drug Discovery Shanghai Institute of Materia Medica Chinese Academy of Sciences  Zhongshan China"},{"name":"Tianfu Jincheng Laboratory  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-7453","authenticated-orcid":false,"given":"Shijie","family":"Chen","sequence":"additional","affiliation":[{"name":"Innovation Center for AI and Drug Discovery School of Pharmacy East China Normal University  Shanghai China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026369729393"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.12.5381"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2010.02.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c01073"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.5c01843"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c13496"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-69663-y"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.6c00113"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c11092"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c16762"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2011.01.077"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2017.04.055"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0163-1_12"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1116"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c00599"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2021.10.005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24006"},{"key":"e_1_2_9_19_1","unstructured":"R.Blake P.Di Lello J.Drummond et al. U.S. Patent US20160272588A1 2016."},{"key":"e_1_2_9_20_1","unstructured":"D. C.Behenna K. D.Freeman\u2010Cook R. L.Hoffman A.Nagata S.Ninkovic andS. C.Sutton World Patent WO2020157652A2 2020."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm800382h"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.05.063"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501963e"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c00721"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2528"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.7b00512"},{"key":"e_1_2_9_27_1","unstructured":"S. M.Pham S.Chakravarty J.Kankanala et al. World Patent WO2021003314A1 2021."},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmcr.2022.100057"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5c00433"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101589\u20101"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010021\u201003536\u2010w"},{"key":"e_1_2_9_32_1","unstructured":"P. V.Reddy N. G.Nair M. A.Smith andW.Kudo World Patent WO2012051296A2 2012."},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011707"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.04.017"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1654"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201065542\u20100"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77386","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:13:45Z","timestamp":1787843625000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":35,"alternative-id":["10.1002\/advs.77386"],"URL":"https:\/\/doi.org\/10.1002\/advs.77386","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"assertion":[{"value":"2026-06-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77386"}}