{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:56:53Z","timestamp":1790657813359,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Selective JAK1 inhibition can control inflammation in immune\u2010mediated diseases with reduced haematological toxicity. IN\u2010115314, a selective JAK1 inhibitor, was evaluated in a first\u2010in\u2010human, randomized, double\u2010blind, placebo\u2010controlled study in healthy participants for safety, pharmacokinetics (PK) and pharmacodynamics (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In six cohorts, participants received IN\u2010115314 or placebo as single oral doses of 2.5 and 10\u2009mg (cohorts 1 and 2) or single and 7\u2010day multiple doses of 25, 50, 100 and 200\u2009mg (cohorts 3\u20136). JAK1 and JAK2 inhibition was evaluated by changes from baseline in IL\u20106\u2013induced phosphorylated STAT1 (pSTAT1) and GM\u2010CSF\u2013induced pSTAT5. PD samples were collected up to 24\u2009h post\u2010dose after a single dose and at steady state, whereas blood and urine PK samples for IN\u2010115314 and IN\u2010116118 were collected up to 72\u2009h, with dose\u2010proportionality assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 55 randomized participants, 54 completed the study. Adverse events occurred in 13 of 44 (29.5%) IN\u2010115314 recipients and 2 of 11 (18.2%) placebo recipients; all were mild, with no serious adverse events. IN\u2010115314 demonstrated significant, dose\u2010dependent JAK1 inhibition, with maximal inhibition (97.5%) at 200\u2009mg. Plasma concentrations and JAK1 inhibition were well described by a sigmoidal\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      model. JAK2 inhibition was minimal, with no relevant changes in absolute neutrophil or reticulocyte counts. IN\u2010115314 was rapidly absorbed and eliminated, with a terminal half\u2010life of 0.57\u20132.46\u2009h, supra\u2010dose\u2010proportional but time\u2010invariant PKs and minimal accumulation (accumulation ratio 1.12\u20131.52).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      IN\u2010115314 was safe, well tolerated and showed rapid, dose\u2010dependent JAK1 inhibition consistent with its PK profile. (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      registration no.: NCT04297865).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70847","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:21:14Z","timestamp":1790655674000},"source":"Crossref","is-referenced-by-count":0,"title":["Safety, pharmacodynamics and pharmacokinetics of a novel JAK1\u2010selective inhibitor, IN\u2010115314, in healthy participants: A first\u2010in\u2010human study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-9954","authenticated-orcid":false,"given":"Ki Young","family":"Huh","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaegu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haerim","family":"Jang","sequence":"additional","affiliation":[{"name":"HK inno.N Corp  Seongnam\u2010si Gyeonggi\u2010do South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Kang","sequence":"additional","affiliation":[{"name":"HK inno.N Corp  Seongnam\u2010si Gyeonggi\u2010do South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u2010Jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-9194","authenticated-orcid":false,"given":"Seung Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine and Hospital  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.09.023"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12164"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010021\u201000726\u20108"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/25785826.2023.2214324"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19580"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2014.05.001"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10071002"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.10.039"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000266\u20106"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.07.010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212595"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/1060028019839650"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare9111575"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010020\u201000548\u20106"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2014.918604"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584\u2010024\u201001153\u20101"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102020\u2010219012"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010022\u201000684\u20101"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.354"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1513"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16176"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2022.2099835"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010015\u20100240\u2010z"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2024.106747"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010023\u201001225\u20107"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13071044"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119889"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1127935"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2023.11.002"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501732"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa893"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2024.2348491"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010022\u201001129\u2010y"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70847","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bcp.70847","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bcp.70847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:21:15Z","timestamp":1790655675000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/bcp.70847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":34,"alternative-id":["10.1002\/bcp.70847"],"URL":"https:\/\/doi.org\/10.1002\/bcp.70847","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"article-number":"bcp.70847"}}