{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:45:44Z","timestamp":1780584344177,"version":"3.54.1"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017291","name":"Zhongshan Science and Technology Bureau","doi-asserted-by":"publisher","award":["CXTD2023009"],"award-info":[{"award-number":["CXTD2023009"]}],"id":[{"id":"10.13039\/501100017291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22271297"],"award-info":[{"award-number":["22271297"]}],"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":["2021QN020533"],"award-info":[{"award-number":["2021QN020533"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.ejmech.2026.118807","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T16:07:40Z","timestamp":1774714060000},"page":"118807","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Active fragment assembly strategy enabling fast discovery of KRAS inhibitors against pancreatic cancer cells"],"prefix":"10.1016","volume":"310","author":[{"given":"Pengli","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghui","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yating","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7666-9550","authenticated-orcid":false,"given":"Guoqin","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118807_bib1","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrd.2016.109","article-title":"Twenty years on: the impact of fragments on drug discovery","volume":"15","author":"Daniel","year":"2016","journal-title":"Nat. Rev. Drug Disc."},{"key":"10.1016\/j.ejmech.2026.118807_bib2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.pharmthera.2016.07.003","article-title":"The ways and means of fragment-based drug design","volume":"167","author":"Bradley","year":"2016","journal-title":"Pharmacol. Therapeut."},{"key":"10.1016\/j.ejmech.2026.118807_bib3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.tips.2021.04.001","article-title":"Fragment-based drug design facilitates selective kinase inhibitor discovery","volume":"42","author":"Wang","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2026.118807_bib4","article-title":"Development of selective class I protein arginine methyltransferase inhibitors through fragment-based drug design approach","volume":"260","author":"Debomita","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib5","doi-asserted-by":"crossref","first-page":"2604","DOI":"10.1021\/acs.jmedchem.8b00057","article-title":"Discovery of novel KRAS-PDE\u03b4 inhibitors by fragment-based drug design","volume":"61","author":"Chen","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib6","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1021\/acs.jmedchem.4c02593","article-title":"Fragment-to-lead medicinal chemistry publications in 2023","volume":"68","author":"Holvey","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib7","doi-asserted-by":"crossref","first-page":"5000","DOI":"10.1021\/acs.jmedchem.5c00424","article-title":"Fragment-based drug design: from then until now, and toward the future","volume":"68","author":"Xu","year":"2025","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrd4163","article-title":"The role of ligand efficiency metrics in drug discovery","volume":"13","author":"Hopkins","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118807_bib9","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/nrd.2016.109","article-title":"Twenty years on: the impact of fragments on drug discovery","volume":"15","author":"Erlanson","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118807_bib10","first-page":"180","article-title":"Application of fragment-based drug discovery to versatile targets. Front Mol","volume":"7","author":"Li","year":"2020","journal-title":"Biosci"},{"key":"10.1016\/j.ejmech.2026.118807_bib11","doi-asserted-by":"crossref","first-page":"518","DOI":"10.3390\/biom10040518","article-title":"A proof-of-concept fragment screening of a hit-validated 96-compounds library against human carbonic anhydrase II","volume":"10","author":"Glockner","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.ejmech.2026.118807_bib12","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/nrc3106","article-title":"RAS oncogenes: weaving a tumorigenic web","volume":"11","author":"Pylayeva-Gupta","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2026.118807_bib13","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1158\/0008-5472.CAN-19-3682","article-title":"The frequency of Ras mutations in cancer","volume":"80","author":"Prior","year":"2020","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejmech.2026.118807_bib14","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nature12796","article-title":"K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions","volume":"503","author":"Ostrem","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118807_bib15","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41586-019-1694-1","article-title":"The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity","volume":"575","author":"Canon","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118807_bib16","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1021\/acs.jmedchem.9b01180","article-title":"Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors","volume":"63","author":"Lanman","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1158\/2159-8290.CD-19-1167","article-title":"The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients","volume":"10","author":"Hallin","year":"2020","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118807_bib18","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1126\/science.abn4180","article-title":"Modulation of the proteostasis network promotes tumor resistance to oncogenic KRAS inhibitors","volume":"381","author":"Lv","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118807_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2019.111691","article-title":"Indole: a privileged scaffold for the design of anti-cancer agents","volume":"183","author":"Wan","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib20","doi-asserted-by":"crossref","first-page":"15823","DOI":"10.1073\/pnas.1904529116","article-title":"Drugging an undruggable pocket on KRAS","volume":"116","author":"Kessler","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ejmech.2026.118807_bib21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.bioorg.2019.02.007","article-title":"Indole derivatives as multifunctional drugs: synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones","volume":"85","author":"Demurtas","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113400","article-title":"An insight in anti-malarial potential of indole scaffold: a review","volume":"218","author":"Chauhan","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib23","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1021\/jm2013248","article-title":"Oxadiazoles in medicinal chemistry","volume":"55","author":"Bostr\u00f6m","year":"2012","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib24","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41586-023-06123-3","article-title":"Pan-KRAS inhibitor disables oncogenic signalling and tumour growth","volume":"619","author":"Kim","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118807_bib25","doi-asserted-by":"crossref","first-page":"14614","DOI":"10.1021\/acs.jmedchem.2c01120","article-title":"Fragment optimization of reversible binding to the switch II pocket on KRAS leads to a potent, in vivo active KRASG12C inhibitor","volume":"65","author":"Br\u00f6ker","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib26","doi-asserted-by":"crossref","first-page":"6949","DOI":"10.1021\/acs.jmedchem.1c00491","article-title":"Thiazolidinedione \u201cmagic bullets\u201d simultaneously targeting PPAR\u03b3 and HDACs: design, synthesis, and investigations of their in vitro and in vivo antitumor effects","volume":"64","author":"Tilekar","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2022.106234","article-title":"Structural optimization of novel Ras modulator for treatment of colorectal cancer by promoting \u03b2-catenin and Ras degradation","volume":"130","author":"Choi","year":"2023","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib28","doi-asserted-by":"crossref","first-page":"20403","DOI":"10.1021\/jacs.3c05899","article-title":"Simultaneous covalent modification of K-Ras(G12D) and K-Ras(G12C) with tunable oxirane electrophiles","volume":"145","author":"Yu","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2026.118807_bib29","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1021\/acs.jmedchem.1c01688","article-title":"Identification of MRTX1133, a noncovalent, potent, and selective KRASG12D inhibitor","volume":"65","author":"Wang","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib30","doi-asserted-by":"crossref","first-page":"545","DOI":"10.4155\/fmc.16.9","article-title":"Advanced molecular dynamics simulation methods for kinase drug discovery","volume":"8","author":"Aci-S\u00e8che","year":"2016","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib31","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1016\/j.apsb.2024.01.020","article-title":"High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation","volume":"14","author":"Fan","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.ejmech.2026.118807_bib32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"10.1016\/j.ejmech.2026.118807_bib33","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.ccell.2018.08.009","article-title":"Overcoming resistance to dual innate immune and MEK inhibition downstream of KRAS","volume":"34","author":"Kitajima","year":"2018","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejmech.2026.118807_bib34","doi-asserted-by":"crossref","first-page":"8569","DOI":"10.1021\/acs.jmedchem.3c02129","article-title":"An improved PDE6D inhibitor combines with sildenafil to inhibit KRAS mutant cancer cell growth","volume":"67","author":"Kaya","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib35","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114243","article-title":"Discovery of Thieno[2,3-d]pyrimidine-based KRAS G12D inhibitors as potential anticancer agents via combinatorial virtual screening","volume":"233","author":"Li","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118807_bib36","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"issue":"2021","key":"10.1016\/j.ejmech.2026.118807_bib37","doi-asserted-by":"crossref","first-page":"W530","DOI":"10.1093\/nar\/gkab294","article-title":"Expanding the scope of the protein\u2013ligand interaction profiler to DNA and RNA","volume":"49","author":"Adasme","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426002527?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426002527?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:56:22Z","timestamp":1778676982000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426002527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":37,"alternative-id":["S0223523426002527"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118807","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Active fragment assembly strategy enabling fast discovery of KRAS inhibitors against pancreatic cancer cells","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118807","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118807"}}