{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:04:03Z","timestamp":1785171843123,"version":"3.55.0"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100019832","name":"Galapagos NV","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019832","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.bmcl.2025.130386","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T22:25:43Z","timestamp":1755987943000},"page":"130386","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Discovery of GLPG4471, a potent and selective IRAK4 inhibitor for the treatment of inflammatory and autoimmune diseases"],"prefix":"10.1016","volume":"129","author":[{"given":"Oscar","family":"Mammoliti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Bonnaterre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Newsome","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhalid","family":"Akkari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"L\u00f3pez-Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Babel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Jary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00ebtitia","family":"Cherel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"De Lemos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mislav","family":"Or\u0161uli\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Komac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0110enana","family":"Vrban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Trottet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Oste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuelle","family":"Wakselman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Borgonovi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Jagerschmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Pereira","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Blanqu\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"Nys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice A.","family":"Kolb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reginald","family":"Brys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Amantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Gosmini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan-Miguel","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Desroy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2025.130386_bb0005","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.bcp.2010.06.020","article-title":"The interleukin-1 receptor-associated kinases: critical regulators of innate immune signalling","volume":"80","author":"Flannery","year":"2010","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bmcl.2025.130386_bb0010","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1038\/s41423-020-0433-8","article-title":"IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion","volume":"18","author":"Umar","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"10.1016\/j.bmcl.2025.130386_bb0015","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1002\/art.41953","article-title":"The Interleukin-1 Receptor-Associated Kinase 4 Inhibitor PF-06650833 Blocks Inflammation in Preclinical Models of Rheumatic Disease and in Humans Enrolled in a Randomized Clinical Trial","volume":"73","author":"Winkler","year":"2021","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.bmcl.2025.130386_bb0020","doi-asserted-by":"crossref","DOI":"10.1111\/cts.13771","article-title":"The oral IRAK4 inhibitors zabedosertib and BAY1830839 suppress local and systemic immune responses in a randomized trial in healthy male volunteers","volume":"17","author":"Jodl","year":"2024","journal-title":"Clin Transl Sci"},{"key":"10.1016\/j.bmcl.2025.130386_bb0025","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abj3289","article-title":"IRAK4 inhibition dampens pathogenic processes driving inflammatory skin diseases","volume":"15","author":"Lavazais","year":"2023","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.bmcl.2025.130386_bb0030","doi-asserted-by":"crossref","DOI":"10.3389\/frhem.2024.1339870","article-title":"Research and clinical updates on IRAK4 and its roles in inflammation and malignancy: themes and highlights from the 1st symposium on IRAK4 in Cancer","volume":"3","author":"Garcia-Manero","year":"2024","journal-title":"Front Hematol"},{"key":"10.1016\/j.bmcl.2025.130386_bb0035","doi-asserted-by":"crossref","first-page":"5521","DOI":"10.1021\/acs.jmedchem.7b00231","volume":"60","author":"Lee","year":"2017","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0040","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1021\/acsmedchemlett.0c00255","article-title":"Discovery of CA-4948, an orally bioavailable IRAK4 inhibitor for treatment of hematologic malignancies","volume":"11","author":"Gummadi","year":"2020","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130386_bb0045","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1021\/acs.jmedchem.3c01714","article-title":"Discovery of IRAK4 Inhibitors BAY1834845 (Zabedosertib) and BAY1830839","volume":"67","author":"Bothe","year":"2024","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0050","doi-asserted-by":"crossref","first-page":"10619","DOI":"10.1021\/acs.jmedchem.5c00463","article-title":"Discovery of Edecesertib (GS-5718): a potent, selective inhibitor of IRAK4","volume":"68","author":"Ammann","year":"2025","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0055","doi-asserted-by":"crossref","first-page":"18022","DOI":"10.1021\/acs.jmedchem.4c01305","article-title":"Discovery of KT-474a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases","volume":"67","author":"Zheng","year":"2024","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0060","doi-asserted-by":"crossref","first-page":"10548","DOI":"10.1021\/acs.jmedchem.3c01823","article-title":"Discovery of KT-413, a targeted protein degrader of IRAK4 and IMiD substrates targeting MYD88 mutant diffuse large B-cell lymphoma","volume":"67","author":"Weiss","year":"2024","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115606","article-title":"The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases","author":"Bai","year":"2023","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0070","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1021\/acsmedchemlett.5b00106","article-title":"Potent and selective Amidopyrazole inhibitors of IRAK4 that are efficacious in a rodent model of inflammation","volume":"6","author":"McElroy","year":"2015","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130386_bb0075","article-title":"Discovery and optimization of a potent and selective indazolamine series of IRAK4 inhibitors","author":"Zhai","year":"2021","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130386_bb0080","doi-asserted-by":"crossref","first-page":"6223","DOI":"10.1021\/acs.jmedchem.9b00439","article-title":"Development of potent and selective Pyrazolopyrimidine IRAK4 inhibitors","volume":"62","author":"Bryan","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0085","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1021\/acsmedchemlett.9b00380","article-title":"Discovery of potent Benzolactam IRAK4 inhibitors with robust in vivo activity","volume":"11","author":"Rajapaksa","year":"2019","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130386_bb0090","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1016\/j.bmcl.2016.07.048","article-title":"Efforts towards the optimization of a bi-aryl class of potent IRAK4 inhibitors","volume":"26","author":"Hanisak","year":"2016","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.bmcl.2025.130386_bb0095","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/j.str.2006.11.001","article-title":"Crystal structures of IRAK-4 kinase in complex with inhibitors: a serine\/threonine kinase with tyrosine as a gatekeeper","volume":"14","author":"Wang","year":"2006","journal-title":"Structure"},{"key":"10.1016\/j.bmcl.2025.130386_bb0100","doi-asserted-by":"crossref","first-page":"6401","DOI":"10.1021\/acs.jmedchem.8b00077","article-title":"Lipophilic efficiency as an important metric in drug design","volume":"61","author":"Johnson","year":"2018","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0105","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/17460441.2024.2368744","article-title":"An update on lipophilic efficiency as an important metric in drug design","volume":"19","author":"Gallego","year":"2024","journal-title":"Expert Opin Drug Discov"},{"key":"10.1016\/j.bmcl.2025.130386_bb0110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4155\/fdd-2019-0004","article-title":"Application of biomimetic HPLC to estimate in vivo behavior of early drug discovery compounds","volume":"1","author":"Valko","year":"2019","journal-title":"Futur Drug Discov"},{"key":"10.1016\/j.bmcl.2025.130386_bb0115","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.1002\/jps.23288","article-title":"Comparative assessment of in vitro-in vivo extrapolation methods used for predicting hepatic metabolic clearance of drugs","volume":"101","author":"Poulin","year":"2012","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.bmcl.2025.130386_bb0120","doi-asserted-by":"crossref","first-page":"12156","DOI":"10.1021\/acs.jmedchem.9b01813","article-title":"Integrating the impact of lipophilicity on potency and pharmacokinetic parameters enables the use of diverse chemical space during small molecule drug optimization","volume":"63","author":"Miller","year":"2020","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2174\/1389200219666180821094502","article-title":"The impact of carboxylesterases in drug metabolism and pharmacokinetics","volume":"20","author":"Di","year":"2019","journal-title":"Curr Drug Metab"},{"key":"10.1016\/j.bmcl.2025.130386_bb0130","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1038\/nprot.2007.173","article-title":"Collagen-induced arthritis","volume":"2","author":"Brand","year":"2007","journal-title":"Nat Protoc"},{"key":"10.1016\/j.bmcl.2025.130386_bb0135","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1002\/art.20709","article-title":"Histone deacetylase inhibitor suppression of autoantibody-mediated arthritis in mice via regulation of p16INK4a and p21(WAF1\/Cip1) expression","volume":"50","author":"Nishida","year":"2004","journal-title":"Arthritis Rheum"},{"key":"10.1016\/j.bmcl.2025.130386_bb0140","doi-asserted-by":"crossref","first-page":"7119","DOI":"10.1021\/jo034456l","article-title":"Highly efficient synthesis of O-(2,4-dinitrophenyl)hydroxylamine. Application to the synthesis of substituted N-benzoyliminopyridinium ylides","volume":"68","author":"Legault","year":"2003","journal-title":"J Organomet Chem"},{"key":"10.1016\/j.bmcl.2025.130386_bb0145","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1021\/jo01269a075","article-title":"Syntheses of fused aromatic heterocycles by 1,3-dipolar addition reactions. 3-Azapyrrocolines","volume":"33","author":"Boekelheide","year":"1968","journal-title":"J Organomet Chem"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X25002951?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X25002951?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:17:50Z","timestamp":1785169070000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X25002951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":29,"alternative-id":["S0960894X25002951"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2025.130386","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of GLPG4471, a potent and selective IRAK4 inhibitor for the treatment of inflammatory and autoimmune diseases","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2025.130386","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"130386"}}