{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:22:10Z","timestamp":1787656930048,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Current long-acting somatostatin analogs control acromegaly and neuroendocrine tumor symptoms, but rely on depot formulations requiring large-bore needle administration, often associated with injection-site pain, nodules, and variable drug release. To address this limitation, we developed TE-8214, a depot-free octreotide analog conjugated to a soluble, dual-fatty-acid albumin-binding module designed to enable prolonged systemic exposure while maintaining a fully aqueous formulation suitable for subcutaneous administration through a fine 30-gauge needle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>TE-8214\u2019s binding to human serum albumin (HSA) and somatostatin receptor 2 (SSTR2), and its receptor-mediated functional activity, were characterized in vitro and compared with octreotide. Pharmacokinetics and pharmacodynamics \u2014 suppression of serotonin, growth hormone, and insulin-like growth factor-1 (IGF-1) \u2014 were assessed in rodents and dogs following single or repeated dosing of TE-8214 or equimolar octreotide. Safety, tolerability, and pharmacokinetics of TE-8214 were then evaluated in a randomized, double-blind, placebo-controlled Phase 1 single-ascending-dose study in healthy adults (0.6\u20134.0 mg), with IGF-1 assessed as an exploratory pharmacodynamic biomarker.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vitro, TE-8214 bound HSA while retaining potent SSTR2-mediated activity comparable to octreotide. In rodents and dogs, TE-8214's albumin binding extended its terminal half-life and enabled sustained suppression of serotonin, growth hormone, and IGF-1, exceeding the duration achieved with equimolar octreotide. In the Phase 1 study, TE-8214 was well-tolerated across all doses tested, with no serious or Grade \u22653 treatment-emergent adverse events, and produced sustained, dose-dependent reductions in IGF-1 consistent with systemic exposure; at the highest dose, IGF-1 fell by 22.5% from baseline and remained suppressed through Day 28.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that a depot-free, aqueous-formulated octreotide analog can achieve prolonged systemic exposure and sustained pharmacodynamic activity following a single dose in healthy volunteers. Although this study was not designed to evaluate therapeutic efficacy, the pharmacokinetic and pharmacodynamic profile of TE-8214 supports further clinical evaluation in patients with neuroendocrine tumors or acromegaly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:related-object>\n                      <jats:ext-link>https:\/\/clinicaltrials.gov\/<\/jats:ext-link>\n                      , identifier NCT06372652.\n                    <\/jats:related-object>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1871977","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:55:50Z","timestamp":1787655350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A long-acting octreotide analog formed by conjugation with a peptide linker modified with two 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