{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:03:48Z","timestamp":1777633428380,"version":"3.51.4"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>This clinical trial aimed to assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of LW402, a preferential JAK1 inhibitor, in healthy participants, so as to provide support for its further development in treating autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study included two phases: a single ascending dose (10\u2013400 mg) with 54 participants and a multiple ascending dose (50\u2013150 mg, b.i.d for 6 days plus a single dose on day 7) with 36 participants. Safety, PK (from timed blood samples), and PD (JAK1\/JAK2 signaling) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No serious adverse events were reported; only mild treatment-emergent adverse events (TEAEs), such as sinus bradycardia and gastrointestinal issues, occurred. LW402 was rapidly absorbed (median t\n                      <jats:sub>max<\/jats:sub>\n                      : 0.42\u20131.0 hours), with slightly super-proportional exposure and minimal accumulation, and preferentially inhibited JAK1-mediated signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>LW402\u2019s favorable safety profile, predictable PK characteristics, and selective JAK1 inhibition collectively support its continued development for the treatment of autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>http:\/\/www.chinadrugtrials.org.cn<\/jats:ext-link>\n                      , identifier CTR20201897.\n                    <\/jats:p>\n                  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