{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:05Z","timestamp":1790776865181,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022QH186"],"award-info":[{"award-number":["ZR2022QH186"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Proprotein convertase subtilisin\/kexin 9 (PCSK9) mediating the degradation of the hepatic low\u2010density lipoprotein receptor (LDLR), has emerged as a novel therapeutic target for the treatment of hyperlipidemia. Herein, to disrupt the protein\u2010protein interactions (PPIs) between PCSK9 and LDLR, a total of 43 compounds were designed and synthesized by structural modification of previous derived PCSK9 inhibitors. In the PCSK9\u2010LDLR PPI interfering test, compounds\n                    <jats:bold>B7<\/jats:bold>\n                    ,\n                    <jats:bold>B23<\/jats:bold>\n                    , and\n                    <jats:bold>B27<\/jats:bold>\n                    showed inhibitory potency with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 8.86\u2009\u03bcM, 3.95\u2009\u03bcM, and 5.02\u2009\u03bcM, respectively, compared with the positive control SBC\u2010115,337 (IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 11.36\u2009\u03bcM). Molecular docking predicted binding mode of compound\n                    <jats:bold>B27<\/jats:bold>\n                    on the PCSK9\u2010LDLR interaction interface, and hydrophobic interactions play an important role in the binding of\n                    <jats:bold>B27<\/jats:bold>\n                    to PCSK9. Moreover, compounds\n                    <jats:bold>B7<\/jats:bold>\n                    ,\n                    <jats:bold>B23<\/jats:bold>\n                    , and especially\n                    <jats:bold>B27<\/jats:bold>\n                    restored the expression of LDLR and increased LDL uptake of HepG2 cell in the presence of PCSK9. Collectively, lead compounds with lipid\u2010lowering potential were developed for further design of PCSK9\u2010LDLR PPI inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70352","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:46:31Z","timestamp":1783921591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Novel PCSK9\u2010LDLR PPI Inhibitors by a Structural Modification Approach"],"prefix":"10.1002","volume":"87","author":[{"given":"Huan","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Pharmacy Shandong Second Medical University Weifang Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Stomatology Shandong Second Medical University Weifang Shandong 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