{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:40:18Z","timestamp":1777394418625,"version":"3.51.4"},"reference-count":0,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2013,10,10]],"date-time":"2013-10-10T00:00:00Z","timestamp":1381363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2013,10,10]]},"abstract":"<jats:p>\n                    \u03b2-site amyloid-\u03b2 protein precursor cleaving enzyme 1 (BACE1) is the first protease and the rate limiting enzyme in the genesis of amyloid-\u03b2 (A\u03b2). This protein remains an important potential disease-modifying target for the development of drugs to treat Alzheimer's disease (AD). We are pursuing potent BACE1 inhibitors in an effort to identify suitable AD drug candidates. Our results have shown that the novel compound VIa exhibits potent inhibitory effects with IC\n                    <jats:sub>50<\/jats:sub>\n                    = 5.9 nM and displays 30.8-fold, 7500-fold and 17533-fold selectivity against the other aspartic proteases BACE2, cathepsin D and renin, respectively. In cellular assays, VIa moderately reduces A\u03b2 production: A\u03b2\n                    <jats:sub>1-40<\/jats:sub>\n                    with an IC\n                    <jats:sub>50<\/jats:sub>\n                    = 143 nM and 1 nM VIa reduced A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    by 40.17%. Concomitant with VIa inhibiting the \u03b2-cleavage of amyloid-\u03b2 protein precursor (A\u03b2PP), VIa increases the production of sA\u03b2PP\u03b1 with an approximate EC\n                    <jats:sub>50<\/jats:sub>\n                    of 16.5 nM. In testing this compound's efficacy in vivo, the oral administration of VIa resulted in a significant decrease in A\u03b2\n                    <jats:sub>1-40<\/jats:sub>\n                    and A\u03b2\n                    <jats:sub>1-42<\/jats:sub>\n                    in the blood of a mouse model of AD by 17.5\u201372.44% and 14.5\u201380.32%, respectively. This indicates that the novel compound VIa is a small, potent, selective, and non-peptidic BACE1 inhibitor.\n                  <\/jats:p>","DOI":"10.3233\/jad-130836","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T06:11:20Z","timestamp":1528092680000},"page":"823-834","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["The Selective BACE1 Inhibitor VIa Reduces Amyloid-\u03b2 Production in Cell and Mouse Models of Alzheimer's Disease"],"prefix":"10.1177","volume":"37","author":[{"given":"Xiaorui","family":"Cheng","sequence":"first","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Gu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Nie","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junping","family":"Cheng","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2013,10,10]]},"container-title":["Journal of Alzheimer\u2019s Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-130836","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JAD-130836","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:03:11Z","timestamp":1777370591000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JAD-130836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,10]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,10,10]]}},"alternative-id":["10.3233\/JAD-130836"],"URL":"https:\/\/doi.org\/10.3233\/jad-130836","relation":{"is-cited-by":[{"id-type":"doi","id":"10.1007\/s12035-016-9783-8","asserted-by":"object"}]},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,10]]}}}