{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T09:41:32Z","timestamp":1792057292262,"version":"4.4.0"},"reference-count":35,"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":[[2027,3,6]],"date-time":"2027-03-06T00:00:00Z","timestamp":1804291200000},"content-version":"am","delay-in-days":278,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"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\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1AG084635"],"award-info":[{"award-number":["RF1AG084635"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.bmc.2026.118612","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T16:58:04Z","timestamp":1772643484000},"page":"118612","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["High-throughput fragment screening identifies a new small molecule scaffold that modulates TREM2 Signaling"],"prefix":"10.1016","volume":"137","author":[{"given":"Natalie","family":"Fuchs","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"El Gaamouch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Nada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moustafa T.","family":"Gabr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmc.2026.118612_bb0005","doi-asserted-by":"crossref","DOI":"10.1016\/j.tips.2025.06.010","article-title":"TREM2 and LAG-3 in cancer and Alzheimer\u2019s disease immunotherapy","author":"Yuan","year":"2025","journal-title":"Trends Pharmacol Sci"},{"issue":"9","key":"10.1016\/j.bmc.2026.118612_bb0010","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41577-023-00837-1","article-title":"The biology of TREM receptors","volume":"23","author":"Colonna","year":"2023","journal-title":"Nat Rev Immunol"},{"issue":"6","key":"10.1016\/j.bmc.2026.118612_bb0015","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.cell.2015.01.049","article-title":"TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model","volume":"160","author":"Wang","year":"2015","journal-title":"Cell"},{"issue":"11","key":"10.1016\/j.bmc.2026.118612_bb0020","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41582-018-0072-1","article-title":"TREM2 - a key player in microglial biology and Alzheimer disease","volume":"14","author":"Ulland","year":"2018","journal-title":"Nat Rev Neurol"},{"key":"10.1016\/j.bmc.2026.118612_bb0025","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.20391","article-title":"Neurodegenerative disease mutations in TREM2 reveal a functional surface and distinct loss-of-function mechanisms","volume":"5","author":"Kober","year":"2016","journal-title":"Elife"},{"issue":"2","key":"10.1016\/j.bmc.2026.118612_bb0030","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa1211851","article-title":"TREM2 variants in Alzheimer's disease","volume":"368","author":"Guerreiro","year":"2013","journal-title":"N Engl J Med"},{"issue":"8","key":"10.1016\/j.bmc.2026.118612_bb0035","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111686","article-title":"Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology","volume":"41","author":"Wood","year":"2022","journal-title":"Cell Rep"},{"key":"10.1016\/j.bmc.2026.118612_bb0040","article-title":"Functional insights from biophysical study of TREM2 interactions with apoE and Abeta(1-42)","author":"Kober","year":"2020","journal-title":"Alzheimers Dement"},{"key":"10.1016\/j.bmc.2026.118612_bb0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.smim.2023.101739","article-title":"TREM2: a new player in the tumor microenvironment","volume":"67","author":"Molgora","year":"2023","journal-title":"Semin Immunol"},{"issue":"5","key":"10.1016\/j.bmc.2026.118612_bb0050","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/s41590-023-01475-4","article-title":"TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer","volume":"24","author":"Park","year":"2023","journal-title":"Nat Immunol"},{"key":"10.1016\/j.bmc.2026.118612_bb0055","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2022.984193","article-title":"The therapeutic potential of TREM2 in cancer","volume":"12","author":"Wolf","year":"2022","journal-title":"Front Oncol"},{"issue":"4","key":"10.1016\/j.bmc.2026.118612_bb0060","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cell.2020.07.013","article-title":"TREM2 modulation remodels the tumor myeloid landscape enhancing anti-PD-1 immunotherapy","volume":"182","author":"Molgora","year":"2020","journal-title":"Cell"},{"issue":"6","key":"10.1016\/j.bmc.2026.118612_bb0065","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.ccell.2024.05.001","article-title":"Distinct roles of TREM2 in central nervous system cancers and peripheral cancers","volume":"42","author":"Zhong","year":"2024","journal-title":"Cancer Cell"},{"issue":"11","key":"10.1016\/j.bmc.2026.118612_bb0070","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/j.jmb.2017.04.004","article-title":"TREM2-ligand interactions in health and disease","volume":"429","author":"Kober","year":"2017","journal-title":"J Mol Biol"},{"issue":"1","key":"10.1016\/j.bmc.2026.118612_bb0075","doi-asserted-by":"crossref","DOI":"10.1186\/s13024-024-00795-9","article-title":"Biophysical mapping of TREM2-ligand interactions reveals shared surfaces for engagement of multiple Alzheimer\u2019s disease ligands","volume":"20","author":"Greven","year":"2025","journal-title":"Mol Neurodegener"},{"issue":"8","key":"10.1016\/j.bmc.2026.118612_bb0080","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1084\/jem.194.8.1111","article-title":"A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells","volume":"194","author":"Bouchon","year":"2001","journal-title":"J Exp Med"},{"issue":"3","key":"10.1016\/j.bmc.2026.118612_bb0085","first-page":"416","article-title":"A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models","volume":"26","author":"van Lengerich","year":"2023","journal-title":"Nat Neurosci"},{"issue":"3","key":"10.1016\/j.bmc.2026.118612_bb0090","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.109844","article-title":"Targeting TREM2 on tumor-associated macrophages enhances immunotherapy","volume":"37","author":"Binnewies","year":"2021","journal-title":"Cell Rep"},{"key":"10.1016\/j.bmc.2026.118612_bb0095","article-title":"Characterization of the first TREM2 small molecule agonist, VG-3927, for clinical development in Alzheimer's disease","volume":"20","author":"Mirescu","year":"2025","journal-title":"Alzheimers Dement"},{"issue":"7","key":"10.1016\/j.bmc.2026.118612_bb0100","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00018-022-04297-z","article-title":"Sulfavant a as the first synthetic TREM2 ligand discloses a homeostatic response of dendritic cells after receptor engagement","volume":"79","author":"Gallo","year":"2022","journal-title":"Cell Mol Life Sci"},{"issue":"5","key":"10.1016\/j.bmc.2026.118612_bb0105","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"},{"issue":"19","key":"10.1016\/j.bmc.2026.118612_bb0110","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/S1359-6446(03)02831-9","article-title":"A 'rule of three' for fragment-based lead discovery?","volume":"8","author":"Congreve","year":"2003","journal-title":"Drug Discov Today"},{"issue":"3","key":"10.1016\/j.bmc.2026.118612_bb0115","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1038\/nchem.217","article-title":"The rise of fragment-based drug discovery","volume":"1","author":"Murray","year":"2009","journal-title":"Nat Chem"},{"key":"10.1016\/j.bmc.2026.118612_bb0120","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fmolb.2020.00180","article-title":"Application of fragment-based drug discovery to versatile targets","volume":"7","author":"Li","year":"2020","journal-title":"Front Mol Biosci"},{"key":"10.1016\/j.bmc.2026.118612_bb0125","doi-asserted-by":"crossref","DOI":"10.1016\/j.slasd.2025.100255","article-title":"TREM2 hit discovery using temperature-related intensity change (TRIC) technology: a proof-of-concept high-throughput screening approach","volume":"35","author":"Fuchs","year":"2025","journal-title":"SLAS Discov"},{"issue":"11","key":"10.1016\/j.bmc.2026.118612_bb0130","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1021\/acsmedchemlett.4c00350","article-title":"From virtual screens to cellular target engagement: new small molecule ligands for the immune checkpoint LAG-3","volume":"15","author":"Fuchs","year":"2024","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmc.2026.118612_bb0135","article-title":"TREM2 activation by first-in-class direct small molecule agonists: DEL screening, optimization, biophysical validation, and functional characterization","author":"Nada","year":"2025","journal-title":"Eur J Med Chem"},{"issue":"8","key":"10.1016\/j.bmc.2026.118612_bb0140","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1021\/acsmedchemlett.5c00299","article-title":"Discovery of a small molecule TREM2 agonist with improved in vitro pharmacokinetic profile and validated target engagement","volume":"16","author":"Yuan","year":"2025","journal-title":"ACS Med Chem Lett"},{"issue":"1","key":"10.1016\/j.bmc.2026.118612_bb0145","doi-asserted-by":"crossref","DOI":"10.3390\/ph15010029","article-title":"Nano differential scanning fluorimetry-based thermal stability screening and optimal buffer selection for immunoglobulin G","volume":"15","author":"Kim","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"issue":"12","key":"10.1016\/j.bmc.2026.118612_bb0150","doi-asserted-by":"crossref","first-page":"22518","DOI":"10.3390\/ijms151222518","article-title":"Intrinsic tryptophan fluorescence in the detection and analysis of proteins: a focus on Forster resonance energy transfer techniques","volume":"15","author":"Ghisaidoobe","year":"2014","journal-title":"Int J Mol Sci"},{"issue":"5","key":"10.1016\/j.bmc.2026.118612_bb0155","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1084\/jem.171.5.1393","article-title":"LAG-3, a novel lymphocyte activation gene closely related to CD4","volume":"171","author":"Triebel","year":"1990","journal-title":"J Exp Med"},{"key":"10.1016\/j.bmc.2026.118612_bb0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2023.111445","article-title":"TREM2 regulates microglial phagocytosis of synapses in innate immune tolerance","volume":"127","author":"Meng","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"10.1016\/j.bmc.2026.118612_bb0165","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1016\/j.csbj.2025.07.003","article-title":"Biophysical characterization of TREM2 missense variants implicated in neurodegenerative disease","volume":"27","author":"Pillai","year":"2025","journal-title":"Comput Struct Biotechnol J"},{"issue":"15","key":"10.1016\/j.bmc.2026.118612_bb0170","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26157057","article-title":"TREM2 in neurodegenerative disorders: mutation Spectrum, pathophysiology, and therapeutic targeting","volume":"26","author":"Yang","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"1","key":"10.1016\/j.bmc.2026.118612_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e41414","article-title":"Extracellular domain of TREM2 possess two distinct ligand recognition sites: insights from machine-learning guided docking and all-atoms molecular dynamics simulations","volume":"11","author":"Mishra","year":"2025","journal-title":"Heliyon"}],"container-title":["Bioorganic &amp; Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089626000684?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0968089626000684?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:58:27Z","timestamp":1779425907000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0968089626000684"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":35,"alternative-id":["S0968089626000684"],"URL":"https:\/\/doi.org\/10.1016\/j.bmc.2026.118612","relation":{},"ISSN":["0968-0896"],"issn-type":[{"value":"0968-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"High-throughput fragment screening identifies a new small molecule scaffold that modulates TREM2 Signaling","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmc.2026.118612","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118612"}}