{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:07:57Z","timestamp":1778738877775,"version":"3.51.4"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.ejmech.2026.118879","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T22:19:49Z","timestamp":1776637189000},"page":"118879","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Benzothiophene-based, orally active PIK3CA H1047R mutant-selective inhibitors for the treatment of HR+\/HER2- breast cancer"],"prefix":"10.1016","volume":"312","author":[{"given":"Sheng","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfeng","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-7694","authenticated-orcid":false,"given":"Biao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanglong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118879_bib1","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1039\/C8SC04498H","article-title":"The mechanism of PI3K\u03b1 activation at the atomic level","volume":"10","author":"Zhang","year":"2019","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.118879_bib2","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1126\/science.296.5573.1655","article-title":"The phosphoinositide 3-Kinase pathway","volume":"296","author":"Cantley","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118879_bib3","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K pathway in human disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2026.118879_bib4","doi-asserted-by":"crossref","DOI":"10.1007\/s12282-024-01567-5","article-title":"PI3K\/AKT\/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer","author":"Zhang","year":"2024","journal-title":"Breast Cancer"},{"key":"10.1016\/j.ejmech.2026.118879_bib5","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.tibs.2021.05.005","article-title":"PI3K functions as a hub in mechanotransduction","volume":"46","author":"Di-Luoffo","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"10.1016\/j.ejmech.2026.118879_bib6","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The phosphatidylinositol 3-KINASE\u2013AKT pathway in human cancer","volume":"2","author":"Vivanco","year":"2002","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ejmech.2026.118879_bib7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.ccr.2005.05.014","article-title":"Mutant PIK3CA promotes cell growth and invasion of human cancer cells","volume":"7","author":"Samuels","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ejmech.2026.118879_bib8","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.cell.2018.02.060","article-title":"Comprehensive characterization of cancer driver genes and mutations","volume":"173","author":"Bailey","year":"2018","journal-title":"Cell"},{"key":"10.1016\/j.ejmech.2026.118879_bib9","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.1096502","article-title":"High frequency of mutations of the PIK3CA gene in human cancers","volume":"304","author":"Samuels","year":"2004","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118879_bib10","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.bbapap.2009.11.020","article-title":"Somatic mutations in PI3K\u03b1: structural basis for enzyme activation and drug design","volume":"1804","author":"Gabelli","year":"2010","journal-title":"Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics"},{"key":"10.1016\/j.ejmech.2026.118879_bib11","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2215621119","article-title":"Cryo-em structures of cancer-specific helical and kinase domain mutations of PI3K\u03b1","volume":"119","author":"Liu","year":"2022","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2026.118879_bib12","doi-asserted-by":"crossref","DOI":"10.1007\/s11030-025-11138-1","article-title":"Understanding the conformational dynamics of PI3K\u03b1 due to helical domain mutations: insights from Markov state model analysis","author":"Jani","year":"2025","journal-title":"Mol. Divers."},{"key":"10.1016\/j.ejmech.2026.118879_bib13","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1003895","article-title":"Investigating the structure and dynamics of the PIK3CA wild-type and H1047R oncogenic mutant","volume":"10","author":"Gkeka","year":"2014","journal-title":"PLoS Comput. Biol."},{"key":"10.1016\/j.ejmech.2026.118879_bib14","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1126\/science.aaw9032","volume":"366","author":"Vasan","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.ejmech.2026.118879_bib15","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.1039\/D0SC01676D","article-title":"PI3K inhibitors: review and new strategies","volume":"11","author":"Zhang","year":"2020","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.118879_bib16","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1056\/NEJMoa1813904","article-title":"Alpelisib for PIK3CA-Mutated, hormone receptor\u2013positive advanced breast cancer","volume":"380","author":"Andr\u00e9","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118879_bib17","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s40265-019-01161-6","article-title":"Alpelisib: first global approval","volume":"79","author":"Markham","year":"2019","journal-title":"Drugs"},{"key":"10.1016\/j.ejmech.2026.118879_bib18","doi-asserted-by":"crossref","first-page":"3741","DOI":"10.1016\/j.bmcl.2013.05.007","article-title":"Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation","volume":"23","author":"Furet","year":"2013","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2026.118879_bib19","article-title":"Alpelisib-induced diabetes mellitus: case report, pharmacodynamics and management considerations","volume":"13","author":"Peris","year":"2022","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.ejmech.2026.118879_bib20","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.annonc.2020.05.001","article-title":"Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer","volume":"31","author":"Rugo","year":"2020","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejmech.2026.118879_bib21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/2159-8290.CD-23-0704","article-title":"Allosteric PI3K\u03b1 inhibition overcomes On-target resistance to orthosteric inhibitors mediated by secondary PIK3CA mutations","volume":"14","author":"Varkaris","year":"2023","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118879_bib22","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nature13001","article-title":"The ensemble nature of allostery","volume":"508","author":"Motlagh","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118879_bib23","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.str.2020.01.010","article-title":"Allosteric activation of PI3K\u03b1 results in dynamic access to catalytically competent conformations","volume":"28","author":"Chakrabarti","year":"2020","journal-title":"Structure"},{"key":"10.1016\/j.ejmech.2026.118879_bib24","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1021\/jp506423e","article-title":"Exploring a Non-ATP pocket for potential allosteric modulation of PI3K\u03b1","volume":"119","author":"Gkeka","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.ejmech.2026.118879_bib25","doi-asserted-by":"crossref","first-page":"4936","DOI":"10.1021\/acs.jmedchem.4c00078","article-title":"Discovery of pyridopyrimidinones that selectively inhibit the H1047R PI3K\u03b1 mutant protein","volume":"67","author":"Ketcham","year":"2024","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118879_bib26","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.bmc.2017.01.012","article-title":"Identification of allosteric binding sites for PI3K\u03b1 oncogenic mutant specific inhibitor design","volume":"25","author":"Miller","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118879_bib27","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1158\/2159-8290.CD-23-0396","article-title":"STX-478, a mutant-selective, allosteric PI3K\u03b1 inhibitor spares metabolic dysfunction and improves therapeutic response in PI3K\u03b1-Mutant xenografts","volume":"13","author":"Buckbinder","year":"2023","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118879_bib28","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1158\/2159-8290.CD-23-0944","article-title":"Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3K\u03b1 inhibitor that decouples antitumor activity from hyperinsulinemia","volume":"14","author":"Varkaris","year":"2023","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ejmech.2026.118879_bib29","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.annonc.2024.08.2266","article-title":"First-in-human results of STX-478, a mutant-selective PI3Ka inhibitor, in advanced solid tumor patients","volume":"35","author":"Montero","year":"2024","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejmech.2026.118879_bib30","doi-asserted-by":"crossref","first-page":"380","DOI":"10.3390\/pharmaceutics15020380","article-title":"Permeability assessment of a high-throughput mucosal platform","volume":"15","author":"Butnarasu","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.ejmech.2026.118879_bib31","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1039\/D1OB00061F","article-title":"Recent advances in the synthesis and reactivity of azetidines: strain-driven character of the four-membered heterocycle","volume":"19","author":"Mughal","year":"2021","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.ejmech.2026.118879_bib32","series-title":"\u03a1\u03b93\u039a\u03b1 INHIBITORS AND METHODS OF USE THEREOF","author":"Boezio","year":"2023"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426003247?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426003247?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T05:12:14Z","timestamp":1778735534000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426003247"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":32,"alternative-id":["S0223523426003247"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118879","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Benzothiophene-based, orally active PIK3CA H1047R mutant-selective inhibitors for the treatment of HR+\/HER2- breast cancer","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118879","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":"118879"}}