{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:18Z","timestamp":1790035218000,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7244316"],"award-info":[{"award-number":["7244316"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2024YFF1207000"],"award-info":[{"award-number":["2024YFF1207000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"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>MT200605 is a novel small\u2010molecule TrkB agonist designed to mimic BDNF for neuroprotection. This first\u2010in\u2010human phase I trial evaluated its safety, tolerability and pharmacokinetics (PK) in healthy volunteers, alongside preclinical data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Preclinical efficacy was assessed in tMCAO rats; PK in healthy rats. The phase I trial was a single\u2010centre, randomized, double\u2010blind, placebo\u2010controlled study comprising single ascending dose (SAD; 0.15\u20131.2\u00a0mg\/kg) and multiple ascending dose (MAD; 0.3\u20131.2\u00a0mg\/kg\/day q12h for 7\u00a0days) phases in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In rats, MT200605 at \u22651.35\u2009mg\/kg improved day 8 survival (peak survival: 79.2%), reduced infarct volume by 59.7% and improved neurological scores, with quantifiable brain exposure supporting central nervous system penetration. In humans (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200960), MT200605 was well tolerated, with all drug\u2010related AEs being mild and self\u2010limiting. Free MT200605 demonstrated dose\u2010proportional PK, whereas total MT200605 exposure increased in a slightly more\u2010than\u2010dose\u2010proportional manner during MAD, with no accumulation (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009&lt;\u20092). Steady\u2010state total AUC at 0.6\u00a0mg\/kg BID (858\u2009h\u00b7ng\/mL) matched the rat efficacious exposure (906\u2009h\u00b7ng\/mL, 5.3% difference). Urinary excretion of total MT200605 was minimal (&lt;4%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MT200605 shows promising preclinical neuroprotection and an acceptable safety profile with predictable PK in humans. A twice\u2010daily intravenous regimen of 0.6\u00a0mg\/kg (1.2\u00a0mg\/kg\/day) is recommended for phase II trials in acute ischaemic stroke patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70834","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:01:36Z","timestamp":1790031696000},"source":"Crossref","is-referenced-by-count":0,"title":["Preclinical and first\u2010in\u2010human phase I trial of MT200605: A novel TrkB agonist for acute ischaemic stroke"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7787-5530","authenticated-orcid":false,"given":"Xiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Research Ward Beijing Friendship Hospital, Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Early Clinical Evaluation of Nucleic Acid Products and Cell Therapy  Beijing 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