{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T12:45:03Z","timestamp":1775997903267,"version":"3.50.1"},"reference-count":82,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 112\u20102320\u2010B\u2010005\u2010010\u2010MY3"],"award-info":[{"award-number":["NSTC 112\u20102320\u2010B\u2010005\u2010010\u2010MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neprilysin (NEP), a zinc\u2010dependent metalloprotease involved in the degradation of bioactive peptides, represents a validated target for heart failure therapeutics. In this study, a pharmacophore\u2010based virtual screening approach combined with biochemical and biophysical assays, alongside molecular dynamics (MD) simulations, was employed to identify novel NEP inhibitors. The pharmacophore model\n                    <jats:bold>Phar\u2010A3D2R1<\/jats:bold>\n                    successfully identified pentagalloylglucose (PGG) and tannic acid as potent inhibitors, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 17.2\u2009\u00b1\u20091.5\u2009\u03bcM and 10.9\u2009\u00b1\u20090.7\u2009\u03bcM, respectively. Local surface plasmon resonance (LSPR) assays confirmed strong binding affinities (KD\u2009=\u20096.2\u2009\u00b1\u20090.4\u2009\u03bcM for PGG and 5.9\u2009\u00b1\u20090.5\u2009\u03bcM for tannic acid). MD simulations revealed stable ligand\u2013enzyme interactions mediated by hydrogen bonding, hydrophobic contacts, electrostatic interactions, and coordination with the catalytic Zn\n                    <jats:sup>2+<\/jats:sup>\n                    ion. Cytotoxicity assessment in HEK293T cells indicated negligible toxicity. These results validate PGG and tannic acid as promising lead compounds for NEP inhibition and provide a basis for further structure\u2010based optimization toward cardiovascular therapeutics.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70247","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T04:40:16Z","timestamp":1770093616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacophore\u2010Based Identification and Molecular Characterization of Potent Neprilysin Inhibitors: Biochemical and Therapeutic Implications for Cardiovascular Diseases"],"prefix":"10.1111","volume":"107","author":[{"given":"Chung\u2010Ting","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi 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