{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:28:28Z","timestamp":1771921708597,"version":"3.50.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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>Objectives<\/jats:title>\n                    <jats:p>This study aims to identify novel small-molecule inhibitors capable of dual targeting of PD-L1 and tubulin, intending to enhance cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A combination of computer-aided virtual screening, molecular docking, homogeneous time-resolved fluorescence (HTRF) assays, tubulin polymerization inhibition assays, and\n                      <jats:italic>in vivo<\/jats:italic>\n                      antitumor assays was utilized to identify compounds with dual-targeting potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compound PP-1 exhibited moderate inhibitory activity against the PD-1\/PD-L1 interaction (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 81.1\u00a0\u00b5M) and showed dose-dependent inhibition of tubulin polymerization (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 70.1\u00a0\u00b5M). Molecular docking analysis further confirmed that PP-1 can effectively bind to both PD-L1 and tubulin at the molecular level, supporting its bifunctional targeting capability. Importantly, compound PP-1 (50\u00a0mg\/kg, P.O.) demonstrated significant antitumor efficacy in a melanoma model, achieving a tumor growth inhibition rate of 42% without apparent systemic toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PP-1 demonstrates dual-target inhibitory activity against both the PD-1\/PD-L1 immune checkpoint and tubulin polymerization, underscoring its potential as a promising lead compound for the development of next-generation dual-functional anticancer agents.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1740903","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:40:52Z","timestamp":1768372852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chalcone-containing dual-targeting PD-L1\/tubulin small molecules: a novel approach for cancer immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingxing","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Provincial Engineering Research Center of Immunotherapy Drugs for Renal Tumors, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Huangshi Key Laboratory of Molecular Diagnostics and Personalized Therapy, Huangshi Loveandhealth Hospital Affiliated Of Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingwei","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shayu","family":"An","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"He","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Du","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Provincial Engineering Research Center of Immunotherapy Drugs for Renal Tumors, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhong","family":"Su","sequence":"additional","affiliation":[{"name":"School of Medicine, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]},{"name":"Hubei Provincial Engineering Research Center of Immunotherapy Drugs for Renal Tumors, Hubei Polytechnic University","place":["Huangshi, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Yao","sequence":"additional","affiliation":[{"name":"Wuchang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan Wuchang Hospital","place":["Wuchang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/s41575-022-00703-w","article-title":"Current developments in gastric cancer: from molecular profiling to treatment strategy","volume":"20","author":"Alsina","year":"2023","journal-title":"Nat. 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