{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:01:26Z","timestamp":1788447686772,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Enteropeptidase is a serine protease localized on the duodenal brush border that catalyzes the conversion of inactive trypsinogen into active trypsin, thereby regulating protein breakdown in the gut. We evaluated the effects of SCO\u2010792, a novel enteropeptidase inhibitor, in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      In vivo inhibition of enteropeptidase was evaluated via an oral protein challenge. Pharmacological effects were evaluated in normal mice, in diet\u2010induced obese (DIO) mice and in obese and diabetic\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A single oral administration of SCO\u2010792 inhibited plasma branched\u2010chain amino acids (BCAAs) in an oral protein challenge test in mice, indicating in vivo inhibition of enteropeptidase. Repeated treatment with SCO\u2010792 induced reduction in food intake and decrease in body weight in DIO and\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice. Plasma FGF21 levels were increased in SCO\u2010792\u2010treated DIO mice, an observation that was probably independent of reduction in food intake. Hyperglycaemia was markedly improved in SCO\u2010792\u2010treated\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice. A hyperinsulinaemic\u2010euglycaemic clamp study revealed improved muscle insulin sensitivity in SCO\u2010792\u2010treated\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice. SCO\u2010792 also improved plasma and liver lipid profiles and decreased plasma alanine transaminase, suggesting a potential treatment for liver diseases. Dietary supplementation with essential amino acids attenuated the effect of SCO\u2010792 on reduction in food intake and decrease in body weight in normal mice, suggesting a pivotal role for enteropeptidase in these biological phenomena.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SCO\u2010792 inhibited enteropeptidase in vivo, reduced food intake, decreased body weight, increased insulin sensitivity, improved glucose and lipid control, and ameliorated liver parameters in mouse models with obesity and\/or diabetes. SCO\u2010792 may exhibit similar effects in patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13799","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T04:14:21Z","timestamp":1559189661000},"page":"2228-2239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["SCO\u2010792, an enteropeptidase inhibitor, improves disease status of diabetes and obesity in mice"],"prefix":"10.1111","volume":"21","author":[{"given":"Hiroaki","family":"Yashiro","sequence":"first","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Hamagami","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Hiyoshi","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Sugama","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Tsuchimori","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuminari","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-6264","authenticated-orcid":false,"given":"Yusuke","family":"Moritoh","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Division Takeda Pharmaceutical Company Limited  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Yamada","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2751-2666","authenticated-orcid":false,"given":"Masanori","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Research and Development Division SCOHIA PHARMA, Inc.  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3282861fd3"},{"key":"e_1_2_8_3_1","first-page":"952","article-title":"A global response to a global problem: the epidemic of overnutrition","volume":"80","author":"Chopra M","year":"2002","journal-title":"Bull World Health Organ"},{"key":"e_1_2_8_4_1","first-page":"940","article-title":"Socioeconomic status and obesity in adult populations of developing countries: a review","volume":"82","author":"Monteiro CA","year":"2004","journal-title":"Bull World Health Organ"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1295684"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuw024"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.15473"},{"key":"e_1_2_8_8_1","first-page":"414","article-title":"Cetilistat, a new lipase inhibitor for the treatment of obesity","volume":"9","author":"Padwal R","year":"2008","journal-title":"Curr Opin Investig Drugs"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2015.1070827"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-007-0055-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.20.4.270.34882"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-206-43728"},{"key":"e_1_2_8_13_1","first-page":"242","article-title":"Enteropeptidase, a type II transmembrane serine protease","volume":"1","author":"Zheng XL","year":"2009","journal-title":"Front Biosci (Elite Ed)"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(89)90133-3"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.50.4.277"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049612"},{"key":"e_1_2_8_17_1","unstructured":"SasakiM KakegawaK KikuchiF IkedaZ NishikawaY.Fused heterocyclic compound.2015; WO2015\/122187."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.1.125"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.01093"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0392"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0816"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2006.318"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365528109182030"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009074"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr500416v"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4057"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.02.002"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1279"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.2527\/jas.2015-0110"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/embo-reports\/kve071"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-8684-7_3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.013821"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2017.08.009"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.13799","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.13799","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.13799","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.13799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:44:24Z","timestamp":1761871464000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.13799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,2]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/dom.13799"],"URL":"https:\/\/doi.org\/10.1111\/dom.13799","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,2]]},"assertion":[{"value":"2019-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}