{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:05:21Z","timestamp":1789855521682,"version":"4.0.1"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) contributes to fibrosis, immunosuppression, and tumor progression, but systemic TGF-\u03b2 inhibition is limited by toxicity and lack of selectivity. This exploratory proof-of-concept study evaluated novel peptides designed to target the TGF-\u03b2 receptor I\/II complex and examined their effects on canonical and noncanonical TGF-\u03b2 signaling in vitro. Peptides 2_5 and 2_6, selected by in silico\u00a0docking of receptor\u2013ligand interface-derived sequences, were tested in human embryonic kidney 293T (HEK293T) cells at 20 and 50 \u03bcM, with the TGF-\u03b2 receptor I inhibitor SD-208 as a reference. Total and phosphorylated SMAD2, SMAD3, extracellular signal-regulated kinase 1\/2 (ERK1\/2), and c-Jun N-terminal kinase (JNK) were assessed by Western blotting and densitometry. Peptide 2_5 showed the strongest activity, reducing total ERK1\/2 by 65% at 50 \u03bcM and phosphorylated ERK1\/2 by 90.4% and 83.4% at 20 and 50 \u03bcM, respectively; SD-208 reduced total and phosphorylated ERK1\/2 by 64.3% and 54.5%, respectively. Peptide 2_5 also reduced total SMAD2 by 81% at 50 \u03bcM, whereas its effect on SMAD2 phosphorylation was inconsistent. Peptide 2_6 showed minimal effects, JNK was largely unaffected, and SMAD3 results were inconclusive because of weak signals. These preliminary findings suggest that peptide 2_5 may differentially modulate TGF-\u03b2 signaling, with a stronger effect on ERK1\/2 than on SMAD2; however, receptor targeting and pathway selectivity require confirmation in fully replicated quantitative studies.<\/jats:p>","DOI":"10.17305\/bb.2026.14724","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:41:37Z","timestamp":1787229697000},"source":"Crossref","is-referenced-by-count":0,"title":["Novel peptide inhibitors targeting the TGF-\u03b2 receptor I\/II complex modulate SMAD and ERK signaling\u00a0&lt;i&gt;in vitro&lt;\/i&gt;"],"prefix":"10.17305","author":[{"given":"Jacek","family":"Plichta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4416-2736","authenticated-orcid":false,"given":"Micha\u0142 Seweryn","family":"Karbownik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Kuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3718-4793","authenticated-orcid":false,"given":"Micha\u0142","family":"Panek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2026,8,20]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/14724\/4303","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/14724\/4303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:00:38Z","timestamp":1789855238000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/14724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":0,"URL":"https:\/\/doi.org\/10.17305\/bb.2026.14724","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}