{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:41:15Z","timestamp":1785285675315,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002380","name":"Hanyang University","doi-asserted-by":"publisher","award":["HY\u2010 202300000001159"],"award-info":[{"award-number":["HY\u2010 202300000001159"]}],"id":[{"id":"10.13039\/501100002380","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>11\u03b2\u2010hydroxysteroid dehydrogenase type 1 (11\u03b2\u2010HSD1), which is an enzyme that converts cortisone to cortisol, plays a role in the regulation of glucose metabolism and inflammation. J2H\u20101702 is a novel 11\u03b2\u2010HSD1 inhibitor, and the inhibition of 11\u03b2\u2010HSD1 has been shown to improve insulin sensitivity, reduce inflammation, and prevent the development of nonalcoholic steatohepatitis (NASH) in preclinical models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of J2H\u20101702 after a single\u2010dose oral administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomised, double\u2010blinded, placebo\u2010controlled, single\u2010dose, dose\u2010escalation study was conducted on 50 healthy volunteers. Blood and urine samples were collected to assess the PK and PD of J2H\u20101702.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The peak plasma concentration of J2H\u20101702 was observed at 2\u20132.9\u2009h after a single\u2010dose oral administration. J2H\u20101702 reduced 11\u03b2\u2010HSD1 activity compared to the placebo at all dose levels. The drug reached its maximal inhibitory effect within 12\u201324\u2009h post\u2010dose administration, and the inhibitory effect was maintained till 1 day after administration of the study drug. The drug showed typical first\u2010order elimination kinetics, with a mean elimination half\u2010life of 9.8\u201314.7\u2009h. Systemic exposure to J2H\u20101702 increased in a dose\u2010dependent manner. J2H\u20101702 was well tolerated after a single oral administration of up to 300\u2009mg. A total of 11 treatment\u2010emergent adverse events (TEAEs) occurred in seven (14%) participants, all of which were mild and resolved spontaneously. The most common TEAE was diarrhoea (8%), followed by dizziness (4%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this study suggest that J2H\u20101702 could be developed as an effective therapeutic option for NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17726","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T08:29:59Z","timestamp":1695630599000},"page":"1132-1142","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["First in human randomised trial of <scp>J2H<\/scp>\u20101702: A novel 11\u03b2\u2010hydroxysteroid dehydrogenase type 1 inhibitor for non\u2010alcoholic steatohepatitis treatment"],"prefix":"10.1111","volume":"58","author":[{"given":"Yun","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy Daegu Catholic University  Gyeongsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Ra","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Hanyang University Seoul Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-9491","authenticated-orcid":false,"given":"Sang Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Hanyang University Seoul Hospital  Seoul Republic of Korea"},{"name":"Department of Pharmacology Hanyang University, College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30251"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2017.08.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.3"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29466"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14355"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.3.8277"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1460061"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17845"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.4.931"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2000.0119"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009\u20101412"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12131"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14112358"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14646"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(13)70170\u20100"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01122"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005452\u2010x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.04.043"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27368"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.10.042"},{"key":"e_1_2_8_23_1","unstructured":"PharmGKB.The pharmacogenomics knowledgebase. 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