{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:40:10Z","timestamp":1792644010561,"version":"4.5.0"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100012540","name":"Guangdong Province Introduction of Innovative R&D Team","doi-asserted-by":"publisher","award":["2024KCXTD012"],"award-info":[{"award-number":["2024KCXTD012"]}],"id":[{"id":"10.13039\/100012540","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82674888"],"award-info":[{"award-number":["82674888"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20250604144930041"],"award-info":[{"award-number":["JCYJ20250604144930041"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["KCXFZ20230731092802004"],"award-info":[{"award-number":["KCXFZ20230731092802004"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012317"],"award-info":[{"award-number":["2024A1515012317"]}],"id":[{"id":"10.13039\/501100021171","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":[[2026,12]]},"DOI":"10.1016\/j.ejmech.2026.119308","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T23:11:10Z","timestamp":1788995470000},"page":"119308","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Conformation-driven design, synthesis and biological evaluation of novel PAK1 inhibitors that downregulate PD-L1 for triple-negative breast cancer therapy"],"prefix":"10.1016","volume":"320","author":[{"given":"Honglei","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupei","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiji","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhendan","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4544-752X","authenticated-orcid":false,"given":"Dahong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.119308_bib1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13058-020-01296-5","article-title":"Triple-negative breast cancer molecular subtyping and treatment progress","volume":"22","author":"Yin","year":"2020","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.ejmech.2026.119308_bib2","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3109\/07357907.2010.483507","article-title":"Triple-negative breast cancer: unique biology and its management","volume":"28","author":"Maegawa","year":"2010","journal-title":"Cancer Invest."},{"key":"10.1016\/j.ejmech.2026.119308_bib3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-pathol-042420-093238","article-title":"Pathogenesis of triple-negative breast cancer","volume":"17","author":"Derakhshan","year":"2022","journal-title":"Annu. Rev. Pathol."},{"key":"10.1016\/j.ejmech.2026.119308_bib4","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.681476","article-title":"Current triple-negative breast cancer subtypes: dissecting the Most aggressive form of breast cancer","volume":"11","author":"Ensenyat-Mendez","year":"2021","journal-title":"Front. Oncol."},{"key":"10.1016\/j.ejmech.2026.119308_bib5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.ctrv.2009.12.002","article-title":"Triple-negative breast cancer: molecular features, pathogenesis, treatment and current lines of research","volume":"36","author":"Bosch","year":"2010","journal-title":"Cancer Treat Rev."},{"key":"10.1016\/j.ejmech.2026.119308_bib6","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2147\/IJWH.S178349","article-title":"Triple-negative breast cancer: current perspective on the evolving therapeutic landscape","volume":"11","author":"Mehanna","year":"2019","journal-title":"Int. J. Womens Health"},{"key":"10.1016\/j.ejmech.2026.119308_bib7","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1002\/j.1460-2075.1995.tb07189.x","article-title":"A novel serine kinase activated by rac1\/CDC42Hs-dependent autophosphorylation is related to PAK65 and STE20","volume":"14","author":"Martin","year":"1995","journal-title":"EMBO J."},{"key":"10.1016\/j.ejmech.2026.119308_bib8","doi-asserted-by":"crossref","first-page":"3986","DOI":"10.1158\/1078-0432.CCR-18-3258","article-title":"Mutational diversity and therapy response in breast cancer: a sequencing analysis in the neoadjuvant GeparSepto trial","volume":"25","author":"Loibl","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2026.119308_bib9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature18003","article-title":"Proteogenomics connects somatic mutations to signalling in breast cancer","volume":"534","author":"Mertins","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.119308_bib10","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1158\/1078-0432.CCR-11-1952","article-title":"Molecular pathways: targeting p21-activated kinase 1 signaling in cancer--opportunities, challenges, and limitations","volume":"18","author":"Eswaran","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ejmech.2026.119308_bib11","doi-asserted-by":"crossref","first-page":"4756","DOI":"10.1038\/s41388-020-1323-3","article-title":"Pak1 maintains epidermal stem cells by regulating Langerhans cells and is required for skin carcinogenesis","volume":"39","author":"Okumura","year":"2020","journal-title":"Oncogene"},{"key":"10.1016\/j.ejmech.2026.119308_bib12","first-page":"670","article-title":"Discovery of a novel selective PAK1\/HDAC6\/HDAC10 inhibitor ZMF-25 that induces mitochondrial metabolic breakdown and autophagy-related cell death in triple-negative","volume":"vol. 8","author":"Zhang","year":"2025"},{"key":"10.1016\/j.ejmech.2026.119308_bib13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41523-023-00556-9","article-title":"Pak1 pathway hyper-activation mediates resistance to endocrine therapy and CDK4\/6 inhibitors in ER+ breast cancer","volume":"9","author":"Belli","year":"2023","journal-title":"NPJ Breast Cancer"},{"key":"10.1016\/j.ejmech.2026.119308_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2015.2","article-title":"p21-activated kinase 1 determines stem-like phenotype and sunitinib resistance via NF-\u03baB\/IL-6 activation in renal cell carcinoma","volume":"6","author":"Zhu","year":"2015","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2026.119308_bib15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11864-021-00833-4","article-title":"Biomarkers of immune checkpoint blockade response in triple-negative breast cancer","volume":"22","author":"Isaacs","year":"2021","journal-title":"Curr. Treat. Options Oncol."},{"key":"10.1016\/j.ejmech.2026.119308_bib16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-981-15-3266-5_3","article-title":"Roles of PD-1\/PD-L1 pathway: Signaling, cancer, and beyond","volume":"1248","author":"Ai","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.ejmech.2026.119308_bib17","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1080\/15384047.2020.1838032","article-title":"Obesity and metabolic syndrome related macrophage promotes PD-L1 expression in TNBC through IL6\/JAK\/STAT pathway and can be reversed by telmisartan","volume":"21","author":"Wang","year":"2020","journal-title":"Cancer Biol. Ther."},{"key":"10.1016\/j.ejmech.2026.119308_bib18","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1080\/13543784.2022.2049232","article-title":"Progress and pitfalls in the use of immunotherapy for patients with triple negative breast cancer","volume":"31","author":"Agostinetto","year":"2022","journal-title":"Expert Opin. Invest. Drugs"},{"key":"10.1016\/j.ejmech.2026.119308_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbadis.2024.167236","article-title":"PAK1 inhibition increases TRIM21-induced PD-L1 degradation and enhances responses to anti-PD-1 therapy in pancreatic cancer","volume":"1870","author":"Wang","year":"2024","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"10.1016\/j.ejmech.2026.119308_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.drup.2025.101288","article-title":"Drug resistance in breast cancer: mechanisms and strategies for management","volume":"83","author":"Wu","year":"2025","journal-title":"Drug Resist. Updates"},{"key":"10.1016\/j.ejmech.2026.119308_bib21","doi-asserted-by":"crossref","first-page":"5671","DOI":"10.1073\/pnas.1219383110","article-title":"Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486","volume":"110","author":"Dolan","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2026.119308_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112220","article-title":"Design, synthesis and biological evaluation of 1H-pyrazolo [3,4-d]pyrimidine derivatives as PAK1 inhibitors that trigger apoptosis, ER stress and anti-migration effect in MDA-MB-231 cells","volume":"194","author":"Zhang","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119308_bib23","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1021\/acsmedchemlett.5b00102","article-title":"Optimization of a dibenzodiazepine hit to a potent and selective allosteric PAK1 inhibitor","volume":"6","author":"Karpov","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.119308_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2025.130307","article-title":"Identification of a p21-activated kinase 1 (PAK1) inhibitor with 10-fold selectivity against PAK2","volume":"127","author":"Johns","year":"2025","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.119308_bib25","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1021\/acsmedchemlett.6b00322","article-title":"Optimization of highly kinase selective bis-anilino pyrimidine PAK1 inhibitors","volume":"7","author":"McCoull","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.119308_bib26","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1126\/science.1095920","article-title":"Protein kinase inhibitors: insights into drug design from structure","volume":"303","author":"Noble","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.119308_bib27","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijbiomac.2023.126348","article-title":"Identification of a novel PAK1\/HDAC6 dual inhibitor ZMF-23 that triggers tubulin-stathmin regulated cell death in triple negative breast cancer","volume":"251","author":"Zhang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.ejmech.2026.119308_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/ctm2.70273","article-title":"Integrated spatial multi-omics profiling of Fusobacterium nucleatum in breast cancer unveils its role in tumour microenvironment modulation and cancer progression","volume":"15","author":"Zhao","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"10.1016\/j.ejmech.2026.119308_bib29","doi-asserted-by":"crossref","first-page":"e414","DOI":"10.1097\/MPA.0000000000002450","article-title":"Transcriptome analysis of human pancreatic stellate cells Co-cultured with PAK1-Modulated cells revealed the role of cytokine pathway in tumor microenvironment","volume":"54","author":"Duggirala","year":"2025","journal-title":"Pancreas"},{"key":"10.1016\/j.ejmech.2026.119308_bib30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12943-023-01850-7","article-title":"Advances in immunotherapy for triple-negative breast cancer","volume":"22","author":"Liu","year":"2023","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.ejmech.2026.119308_bib31","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2025.217865","article-title":"The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): emerging therapeutic opportunities","volume":"628","author":"Sabit","year":"2025","journal-title":"Cancer Lett."},{"key":"10.1016\/j.ejmech.2026.119308_bib32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/cac2.12416","article-title":"Tumor microenvironment signaling and therapeutics in cancer progression","volume":"43","author":"Goenka","year":"2023","journal-title":"Cancer Commun."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426007531?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426007531?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:25:09Z","timestamp":1792643109000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426007531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":32,"alternative-id":["S0223523426007531"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119308","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Conformation-driven design, synthesis and biological evaluation of novel PAK1 inhibitors that downregulate PD-L1 for triple-negative breast cancer therapy","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119308","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":"119308"}}