{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:50:54Z","timestamp":1792785054173,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":94,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Geneva","id":[{"id":"https:\/\/ror.org\/01swzsf04","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Myocardial infarction necessitates rapid reperfusion to limit ischemic damage. However, reperfusion itself exacerbates cardiomyocyte death and the inflammatory response. ATP release through pannexin1 (Panx1) channels is a key driver of leukocyte recruitment, yet most Panx1 channel inhibitors lack specificity or in vivo stability. We previously developed a macrocyclic peptidomimetic targeting the first extracellular loop (EL1) of Panx1, SBL-PX1-42, which demonstrated anti-inflammatory activity and high plasma stability in vitro. Here, we generated EL2 peptidomimetics, identified SBL-PX1-213 as a lead compound, and assessed its cardioprotective potential alone or combined with SBL-PX1-42 in experimental cardiac ischemia\/reperfusion (I\/R). In Langendorff-perfused wild-type (WT) hearts, SBL-PX1-42, SBL-PX1-213, and their combination did not affect baseline cardiac function, indicating absence of cardiotoxicity. In vivo I\/R, induced by transient (30\u00a0min) coronary artery ligation and 24\u00a0h reperfusion, was performed in WT and\n                    <jats:italic>Panx1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Intravenous administration of either compound at reperfusion reduced infarct size in WT animals. In\n                    <jats:italic>Panx1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, SBL-PX1-213 and the combination remained cardioprotective, whereas SBL-PX1-42 lost efficacy, supporting its Panx1-dependent activity. None of the treatments affected blood cell counts, suggesting the absence of unwanted side effects on circulating cells. These findings establish SBL-PX1-42 and SBL-PX1-213 as cardioprotective agents acting through both Panx1-dependent and Panx1-independent mechanisms.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-61614-3","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T15:14:51Z","timestamp":1783782891000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pannexin1-dependent and -independent protection by novel peptidomimetics against cardiac ischemia\/reperfusion injury"],"prefix":"10.1038","volume":"16","author":[{"given":"Malaury","family":"Tournier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lamouroux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laureano E.","family":"Carpio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Bes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Iaculli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maral","family":"Azam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Gozalbes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Molica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Ballet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-0044","authenticated-orcid":false,"given":"Brenda R.","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"61614_CR1","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1093\/eurheartj\/ehae466","volume":"45","author":"A Timmis","year":"2024","unstructured":"Timmis, A. et al. European Society of Cardiology: the 2023 Atlas of Cardiovascular Disease Statistics. Eur. Heart J. 45, 4019\u20134062. https:\/\/doi.org\/10.1093\/eurheartj\/ehae466 (2024).","journal-title":"Eur. Heart J."},{"key":"61614_CR2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1172\/JCI62874","volume":"123","author":"DJ Hausenloy","year":"2013","unstructured":"Hausenloy, D. J. & Yellon, D. M. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J. Clin. Invest. 123, 92\u2013100. https:\/\/doi.org\/10.1172\/JCI62874 (2013).","journal-title":"J. Clin. Invest."},{"key":"61614_CR3","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41569-020-0403-y","volume":"17","author":"G Heusch","year":"2020","unstructured":"Heusch, G. Myocardial ischaemia-reperfusion injury and cardioprotection in perspective. Nat. Rev. Cardiol. 17, 773\u2013789. https:\/\/doi.org\/10.1038\/s41569-020-0403-y (2020).","journal-title":"Nat. Rev. Cardiol."},{"key":"61614_CR4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jacc.2018.09.086","volume":"73","author":"SM Davidson","year":"2019","unstructured":"Davidson, S. M. et al. Multitarget Strategies to Reduce Myocardial Ischemia\/Reperfusion Injury: JACC Review Topic of the Week. J. Am. Coll. Cardiol. 73, 89\u201399. https:\/\/doi.org\/10.1016\/j.jacc.2018.09.086 (2019).","journal-title":"J. Am. Coll. Cardiol."},{"key":"61614_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1124\/pharmrev.121.000348","volume":"75","author":"P Ferdinandy","year":"2023","unstructured":"Ferdinandy, P. et al. Interaction of Cardiovascular Nonmodifiable Risk Factors, Comorbidities and Comedications With Ischemia\/Reperfusion Injury and Cardioprotection by Pharmacological Treatments and Ischemic Conditioning. Pharmacol. Rev. 75, 159\u2013216. https:\/\/doi.org\/10.1124\/pharmrev.121.000348 (2023).","journal-title":"Pharmacol. Rev."},{"key":"61614_CR6","doi-asserted-by":"publisher","unstructured":"Francisco, J. & Del Re, D. P. Inflammation in Myocardial Ischemia\/Reperfusion Injury: Underlying Mechanisms and Therapeutic Potential. Antioxid. (Basel). 12 https:\/\/doi.org\/10.3390\/antiox12111944 (2023).","DOI":"10.3390\/antiox12111944"},{"key":"61614_CR7","doi-asserted-by":"publisher","first-page":"102894","DOI":"10.1016\/j.redox.2023.102894","volume":"67","author":"G Heusch","year":"2023","unstructured":"Heusch, G. et al. Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection. Redox Biol. 67, 102894. https:\/\/doi.org\/10.1016\/j.redox.2023.102894 (2023).","journal-title":"Redox Biol."},{"key":"61614_CR8","doi-asserted-by":"publisher","first-page":"926895","DOI":"10.3389\/fimmu.2022.926895","volume":"13","author":"S Ghafouri-Fard","year":"2022","unstructured":"Ghafouri-Fard, S. et al. NLRP3: Role in ischemia\/reperfusion injuries. Front. Immunol. 13, 926895. https:\/\/doi.org\/10.3389\/fimmu.2022.926895 (2022).","journal-title":"Front. Immunol."},{"key":"61614_CR9","doi-asserted-by":"publisher","first-page":"10555","DOI":"10.1038\/ncomms10555","volume":"7","author":"M Karmakar","year":"2016","unstructured":"Karmakar, M., Katsnelson, M. A., Dubyak, G. R. & Pearlman, E. Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nat. Commun. 7, 10555. https:\/\/doi.org\/10.1038\/ncomms10555 (2016).","journal-title":"Nat. Commun."},{"key":"61614_CR10","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1038\/nature09413","volume":"467","author":"FB Chekeni","year":"2010","unstructured":"Chekeni, F. B. et al. Pannexin 1 channels mediate \u2018find-me\u2019 signal release and membrane permeability during apoptosis. Nature 467, 863\u2013867. https:\/\/doi.org\/10.1038\/nature09413 (2010).","journal-title":"Nature"},{"key":"61614_CR11","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bbamcr.2016.10.006","volume":"1864","author":"S Crespo Yanguas","year":"2017","unstructured":"Crespo Yanguas, S. et al. Pannexin1 as mediator of inflammation and cell death. Biochim. Biophys. Acta Mol. Cell. Res. 1864, 51\u201361. https:\/\/doi.org\/10.1016\/j.bbamcr.2016.10.006 (2017).","journal-title":"Biochim. Biophys. Acta Mol. Cell. Res."},{"key":"61614_CR12","doi-asserted-by":"publisher","first-page":"1020826","DOI":"10.3389\/fcell.2022.1020826","volume":"10","author":"OM Rusiecka","year":"2022","unstructured":"Rusiecka, O. M., Tournier, M., Molica, F. & Kwak, B. R. Pannexin1 channels-a potential therapeutic target in inflammation. Front. Cell. Dev. Biol. 10, 1020826. https:\/\/doi.org\/10.3389\/fcell.2022.1020826 (2022).","journal-title":"Front. Cell. Dev. Biol."},{"key":"61614_CR13","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1085\/jgp.201711888","volume":"150","author":"YH Chiu","year":"2018","unstructured":"Chiu, Y. H., Schappe, M. S., Desai, B. N. & Bayliss, D. A. Revisiting multimodal activation and channel properties of Pannexin 1. J. Gen. Physiol. 150, 19\u201339. https:\/\/doi.org\/10.1085\/jgp.201711888 (2018).","journal-title":"J. Gen. Physiol."},{"key":"61614_CR14","doi-asserted-by":"publisher","unstructured":"Dahl, G. ATP release through pannexon channels. Philos. Trans. R Soc. Lond. B Biol. Sci. 370 https:\/\/doi.org\/10.1098\/rstb.2014.0191 (2015).","DOI":"10.1098\/rstb.2014.0191"},{"key":"61614_CR15","doi-asserted-by":"publisher","first-page":"7965","DOI":"10.1038\/ncomms8965","volume":"6","author":"AW Lohman","year":"2015","unstructured":"Lohman, A. W. et al. Pannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation. Nat. Commun. 6, 7965. https:\/\/doi.org\/10.1038\/ncomms8965 (2015).","journal-title":"Nat. Commun."},{"key":"61614_CR16","doi-asserted-by":"publisher","unstructured":"Chen, K. W. et al. Extrinsic and intrinsic apoptosis activate pannexin-1 to drive NLRP3 inflammasome assembly. EMBO J. 38 https:\/\/doi.org\/10.15252\/embj.2019101638 (2019).","DOI":"10.15252\/embj.2019101638"},{"key":"61614_CR17","doi-asserted-by":"publisher","first-page":"5071","DOI":"10.1038\/sj.emboj.7601378","volume":"25","author":"P Pelegrin","year":"2006","unstructured":"Pelegrin, P. & Surprenant, A. Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J. 25, 5071\u20135082. https:\/\/doi.org\/10.1038\/sj.emboj.7601378 (2006).","journal-title":"EMBO J."},{"key":"61614_CR18","doi-asserted-by":"publisher","first-page":"18143","DOI":"10.1074\/jbc.M109.004804","volume":"284","author":"WR Silverman","year":"2009","unstructured":"Silverman, W. R. et al. The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J. Biol. Chem. 284, 18143\u201318151. https:\/\/doi.org\/10.1074\/jbc.M109.004804 (2009).","journal-title":"J. Biol. Chem."},{"key":"61614_CR19","doi-asserted-by":"publisher","unstructured":"Good, M. E. et al. Endothelial cell Pannexin1 modulates severity of ischemic stroke by regulating cerebral inflammation and myogenic tone. JCI Insight. 3 https:\/\/doi.org\/10.1172\/jci.insight.96272 (2018).","DOI":"10.1172\/jci.insight.96272"},{"key":"61614_CR20","doi-asserted-by":"publisher","first-page":"2342","DOI":"10.1093\/cvr\/cvad120","volume":"119","author":"OM Rusiecka","year":"2023","unstructured":"Rusiecka, O. M. et al. Mitochondrial pannexin1 controls cardiac sensitivity to ischaemia\/reperfusion injury. Cardiovasc. Res. 119, 2342\u20132354. https:\/\/doi.org\/10.1093\/cvr\/cvad120 (2023).","journal-title":"Cardiovasc. Res."},{"key":"61614_CR21","doi-asserted-by":"publisher","first-page":"L301","DOI":"10.1152\/ajplung.00004.2018","volume":"315","author":"AK Sharma","year":"2018","unstructured":"Sharma, A. K. et al. Pannexin-1 channels on endothelial cells mediate vascular inflammation during lung ischemia-reperfusion injury. Am. J. Physiol. Lung Cell. Mol. Physiol. 315, L301\u2013L312. https:\/\/doi.org\/10.1152\/ajplung.00004.2018 (2018).","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"61614_CR22","doi-asserted-by":"publisher","first-page":"19395","DOI":"10.1074\/jbc.RA119.010949","volume":"294","author":"L Su","year":"2019","unstructured":"Su, L. et al. Pannexin 1 mediates ferroptosis that contributes to renal ischemia\/reperfusion injury. J. Biol. Chem. 294, 19395\u201319404. https:\/\/doi.org\/10.1074\/jbc.RA119.010949 (2019).","journal-title":"J. Biol. Chem."},{"key":"61614_CR23","doi-asserted-by":"publisher","first-page":"36973","DOI":"10.18632\/oncotarget.16937","volume":"8","author":"M Freitas-Andrade","year":"2017","unstructured":"Freitas-Andrade, M., Bechberger, J. F., MacVicar, B. A., Viau, V. & Naus, C. C. Pannexin1 knockout and blockade reduces ischemic stroke injury in female, but not in male mice. Oncotarget 8, 36973\u201336983. https:\/\/doi.org\/10.18632\/oncotarget.16937 (2017).","journal-title":"Oncotarget"},{"key":"61614_CR24","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1161\/CIRCRESAHA.120.317272","volume":"128","author":"ME Good","year":"2021","unstructured":"Good, M. E. et al. Endothelial Pannexin 1 Regulates Cardiac Response to Myocardial Infarction. Circ. Res. 128, 1211\u20131213. https:\/\/doi.org\/10.1161\/CIRCRESAHA.120.317272 (2021).","journal-title":"Circ. Res."},{"key":"61614_CR25","doi-asserted-by":"publisher","first-page":"120933","DOI":"10.1016\/j.lfs.2022.120933","volume":"308","author":"WH El-Maadawy","year":"2022","unstructured":"El-Maadawy, W. H., Hassan, M., Badawy, M. H., AbuSeada, A. & Hafiz, E. Probenecid induces the recovery of renal ischemia\/reperfusion injury via the blockade of Pannexin 1\/P2X7 receptor axis. Life Sci. 308, 120933. https:\/\/doi.org\/10.1016\/j.lfs.2022.120933 (2022).","journal-title":"Life Sci."},{"key":"61614_CR26","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.tcb.2016.06.003","volume":"26","author":"JL Esseltine","year":"2016","unstructured":"Esseltine, J. L. & Laird, D. W. Next-Generation Connexin and Pannexin Cell Biology. Trends Cell. Biol. 26, 944\u2013955. https:\/\/doi.org\/10.1016\/j.tcb.2016.06.003 (2016).","journal-title":"Trends Cell. Biol."},{"key":"61614_CR27","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1038\/s41586-020-2357-y","volume":"584","author":"Z Ruan","year":"2020","unstructured":"Ruan, Z., Orozco, I. J., Du, J. & Lu, W. Structures of human pannexin 1 reveal ion pathways and mechanism of gating. Nature 584, 646\u2013651. https:\/\/doi.org\/10.1038\/s41586-020-2357-y (2020).","journal-title":"Nature"},{"key":"61614_CR28","doi-asserted-by":"publisher","unstructured":"Michalski, K. et al. The Cryo-EM structure of pannexin 1 reveals unique motifs for ion selection and inhibition. Elife 9 https:\/\/doi.org\/10.7554\/eLife.54670 (2020).","DOI":"10.7554\/eLife.54670"},{"key":"61614_CR29","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1080\/17460441.2020.1773787","volume":"15","author":"A Caufriez","year":"2020","unstructured":"Caufriez, A., Bock, D., Martin, C., Ballet, S. & Vinken, M. Peptide-based targeting of connexins and pannexins for therapeutic purposes. Expert Opin. Drug Discov. 15, 1213\u20131222. https:\/\/doi.org\/10.1080\/17460441.2020.1773787 (2020).","journal-title":"Expert Opin. Drug Discov"},{"key":"61614_CR30","doi-asserted-by":"publisher","first-page":"13086","DOI":"10.1021\/acs.jmedchem.3c01116","volume":"66","author":"A Lamouroux","year":"2023","unstructured":"Lamouroux, A. et al. Structure-Based Design and Synthesis of Stapled (10)Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases. J. Med. Chem. 66, 13086\u201313102. https:\/\/doi.org\/10.1021\/acs.jmedchem.3c01116 (2023).","journal-title":"J. Med. Chem."},{"key":"61614_CR31","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1007\/s00204-016-1885-6","volume":"91","author":"M Maes","year":"2017","unstructured":"Maes, M. et al. Inhibition of pannexin1 channels alleviates acetaminophen-induced hepatotoxicity. Arch. Toxicol. 91, 2245\u20132261. https:\/\/doi.org\/10.1007\/s00204-016-1885-6 (2017).","journal-title":"Arch. Toxicol."},{"key":"61614_CR32","doi-asserted-by":"publisher","first-page":"106612","DOI":"10.1016\/j.bioorg.2023.106612","volume":"138","author":"A Caufriez","year":"2023","unstructured":"Caufriez, A. et al. Determination of structural features that underpin the pannexin1 channel inhibitory activity of the peptide (10)Panx1. Bioorg. Chem. 138, 106612. https:\/\/doi.org\/10.1016\/j.bioorg.2023.106612 (2023).","journal-title":"Bioorg. Chem."},{"key":"61614_CR33","doi-asserted-by":"publisher","first-page":"4313","DOI":"10.1091\/mbc.e09-01-0067","volume":"20","author":"S Penuela","year":"2009","unstructured":"Penuela, S., Bhalla, R., Nag, K. & Laird, D. W. Glycosylation regulates pannexin intermixing and cellular localization. Mol. Biol. Cell. 20, 4313\u20134323. https:\/\/doi.org\/10.1091\/mbc.e09-01-0067 (2009).","journal-title":"Mol. Biol. Cell."},{"key":"61614_CR34","doi-asserted-by":"publisher","first-page":"C1112","DOI":"10.1152\/ajpcell.00097.2007","volume":"293","author":"J Wang","year":"2007","unstructured":"Wang, J., Ma, M., Locovei, S., Keane, R. W. & Dahl, G. Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am. J. Physiol. Cell. Physiol. 293, C1112\u20131119. https:\/\/doi.org\/10.1152\/ajpcell.00097.2007 (2007).","journal-title":"Am. J. Physiol. Cell. Physiol."},{"key":"61614_CR35","doi-asserted-by":"publisher","first-page":"e70029","DOI":"10.1002\/psc.70029","volume":"31","author":"D Iaculli","year":"2025","unstructured":"Iaculli, D. & Ballet, S. Discovery of Bioactive Peptides Through Peptide Scanning. J. Pept. Sci. 31, e70029. https:\/\/doi.org\/10.1002\/psc.70029 (2025).","journal-title":"J. Pept. Sci."},{"key":"61614_CR36","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s00441-025-03994-y","volume":"402","author":"OM Rusiecka","year":"2025","unstructured":"Rusiecka, O. M. et al. Nanobody-based Pannexin1 channel inhibitors increase survival after cardiac ischemia\/reperfusion. Cell. Tissue Res. 402, 121\u2013137. https:\/\/doi.org\/10.1007\/s00441-025-03994-y (2025).","journal-title":"Cell. Tissue Res."},{"key":"61614_CR37","doi-asserted-by":"publisher","first-page":"22650","DOI":"10.1074\/jbc.M113.476283","volume":"288","author":"Y Bao","year":"2013","unstructured":"Bao, Y., Chen, Y., Ledderose, C., Li, L. & Junger, W. G. Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils. J. Biol. Chem. 288, 22650\u201322657. https:\/\/doi.org\/10.1074\/jbc.M113.476283 (2013).","journal-title":"J. Biol. Chem."},{"key":"61614_CR38","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/s41594-020-0401-0","volume":"27","author":"Z Deng","year":"2020","unstructured":"Deng, Z. et al. Cryo-EM structures of the ATP release channel pannexin 1. Nat. Struct. Mol. Biol. 27, 373\u2013381. https:\/\/doi.org\/10.1038\/s41594-020-0401-0 (2020).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"61614_CR39","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41421-021-00259-0","volume":"7","author":"S Zhang","year":"2021","unstructured":"Zhang, S. et al. Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis. Cell. Discov. 7, 30. https:\/\/doi.org\/10.1038\/s41421-021-00259-0 (2021).","journal-title":"Cell. Discov"},{"key":"61614_CR40","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1161\/01.atv.18.8.1292","volume":"18","author":"M Tamaru","year":"1998","unstructured":"Tamaru, M. et al. Interleukin-1beta induces tissue- and cell type-specific expression of adhesion molecules in vivo. Arterioscler. Thromb. Vasc Biol. 18, 1292\u20131303. https:\/\/doi.org\/10.1161\/01.atv.18.8.1292 (1998).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"61614_CR41","doi-asserted-by":"publisher","first-page":"7874","DOI":"10.1021\/jm5006463","volume":"57","author":"A Anighoro","year":"2014","unstructured":"Anighoro, A., Bajorath, J. & Rastelli, G. Polypharmacology: challenges and opportunities in drug discovery. J. Med. Chem. 57, 7874\u20137887. https:\/\/doi.org\/10.1021\/jm5006463 (2014).","journal-title":"J. Med. Chem."},{"key":"61614_CR42","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nchembio.118","volume":"4","author":"AL Hopkins","year":"2008","unstructured":"Hopkins, A. L. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 4, 682\u2013690. https:\/\/doi.org\/10.1038\/nchembio.118 (2008).","journal-title":"Nat. Chem. Biol."},{"key":"61614_CR43","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","volume":"20","author":"K Fosgerau","year":"2015","unstructured":"Fosgerau, K. & Hoffmann, T. Peptide therapeutics: current status and future directions. Drug Discov Today. 20, 122\u2013128. https:\/\/doi.org\/10.1016\/j.drudis.2014.10.003 (2015).","journal-title":"Drug Discov Today"},{"key":"61614_CR44","doi-asserted-by":"publisher","first-page":"8955","DOI":"10.1021\/jm400856t","volume":"56","author":"JU Peters","year":"2013","unstructured":"Peters, J. U. Polypharmacology - foe or friend? J. Med. Chem. 56, 8955\u20138971. https:\/\/doi.org\/10.1021\/jm400856t (2013).","journal-title":"J. Med. Chem."},{"key":"61614_CR45","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1056\/NEJMra071667","volume":"357","author":"DM Yellon","year":"2007","unstructured":"Yellon, D. M. & Hausenloy, D. J. Myocardial reperfusion injury. N Engl. J. Med. 357, 1121\u20131135. https:\/\/doi.org\/10.1056\/NEJMra071667 (2007).","journal-title":"N Engl. J. Med."},{"key":"61614_CR46","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1042\/BST0350767","volume":"35","author":"J Howl","year":"2007","unstructured":"Howl, J., Nicholl, I. D. & Jones, S. The many futures for cell-penetrating peptides: how soon is now? Biochem. Soc. Trans. 35, 767\u2013769. https:\/\/doi.org\/10.1042\/BST0350767 (2007).","journal-title":"Biochem. Soc. Trans."},{"key":"61614_CR47","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1213\/ANE.0000000000005243","volume":"131","author":"C Torregroza","year":"2020","unstructured":"Torregroza, C. et al. Perioperative Cardioprotection: General Mechanisms and Pharmacological Approaches. Anesth. Analg. 131, 1765\u20131780. https:\/\/doi.org\/10.1213\/ANE.0000000000005243 (2020).","journal-title":"Anesth. Analg"},{"key":"61614_CR48","doi-asserted-by":"publisher","first-page":"41575","DOI":"10.1038\/s41598-025-25477-4","volume":"15","author":"L Boutin","year":"2025","unstructured":"Boutin, L. et al. Galectin-3\/CD146 interaction promotes renal damage and systemic inflammation after acute kidney injury. Sci. Rep. 15, 41575. https:\/\/doi.org\/10.1038\/s41598-025-25477-4 (2025).","journal-title":"Sci. Rep."},{"key":"61614_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00109-025-02617-x","volume":"104","author":"B Mierzejewski","year":"2025","unstructured":"Mierzejewski, B., Kulma, D. & Brzoska, E. The multifaceted roles of MCAM in development, homeostasis, pathological conditions, and cancer. J. Mol. Med. (Berl). 104, 1. https:\/\/doi.org\/10.1007\/s00109-025-02617-x (2025).","journal-title":"J. Mol. Med. (Berl)"},{"key":"61614_CR50","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s00232-011-9393-3","volume":"244","author":"S Bunse","year":"2011","unstructured":"Bunse, S. et al. Single cysteines in the extracellular and transmembrane regions modulate pannexin 1 channel function. J. Membr. Biol. 244, 21\u201333. https:\/\/doi.org\/10.1007\/s00232-011-9393-3 (2011).","journal-title":"J. Membr. Biol."},{"key":"61614_CR51","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1038\/s42003-025-07615-w","volume":"8","author":"AS Rathore","year":"2025","unstructured":"Rathore, A. S., Kumar, N., Choudhury, S., Mehta, N. K. & Raghava, G. P. Prediction of hemolytic peptides and their hemolytic concentration. Commun. Biol. 8, 176. https:\/\/doi.org\/10.1038\/s42003-025-07615-w (2025).","journal-title":"Commun. Biol."},{"key":"61614_CR52","doi-asserted-by":"publisher","first-page":"20772","DOI":"10.1073\/pnas.1018262108","volume":"108","author":"P Bargiotas","year":"2011","unstructured":"Bargiotas, P. et al. Pannexins in ischemia-induced neurodegeneration. Proc. Natl. Acad. Sci. U S A. 108, 20772\u201320777. https:\/\/doi.org\/10.1073\/pnas.1018262108 (2011).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"61614_CR53","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1160\/TH14-11-0981","volume":"114","author":"F Molica","year":"2015","unstructured":"Molica, F. et al. Functional role of a polymorphism in the Pannexin1 gene in collagen-induced platelet aggregation. Thromb. Haemost. 114, 325\u2013336. https:\/\/doi.org\/10.1160\/TH14-11-0981 (2015).","journal-title":"Thromb. Haemost"},{"key":"61614_CR54","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1021\/acsmedchemlett.8b00105","volume":"9","author":"A De Prins","year":"2018","unstructured":"De Prins, A. et al. Synthesis and in Vitro Evaluation of Stabilized and Selective Neuromedin U-1 Receptor Agonists. ACS Med. Chem. Lett. 9, 496\u2013501. https:\/\/doi.org\/10.1021\/acsmedchemlett.8b00105 (2018).","journal-title":"ACS Med. Chem. Lett."},{"key":"61614_CR55","doi-asserted-by":"publisher","first-page":"3562","DOI":"10.1096\/fj.07-8450com","volume":"21","author":"N Hostettler","year":"2007","unstructured":"Hostettler, N. et al. P-selectin- and heparanase-dependent antimetastatic activity of non-anticoagulant heparins. FASEB J. 21, 3562\u20133572. https:\/\/doi.org\/10.1096\/fj.07-8450com (2007).","journal-title":"FASEB J."},{"key":"61614_CR56","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.freeradbiomed.2015.05.023","volume":"86","author":"T Seredenina","year":"2015","unstructured":"Seredenina, T. et al. A subset of N-substituted phenothiazines inhibits NADPH oxidases. Free Radic Biol. Med. 86, 239\u2013249. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2015.05.023 (2015).","journal-title":"Free Radic Biol. Med."},{"key":"61614_CR57","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/bio.1091","volume":"24","author":"A Ashkenazi","year":"2009","unstructured":"Ashkenazi, A. & Marks, R. S. Luminol-dependent chemiluminescence of human phagocyte cell lines: comparison between DMSO differentiated PLB 985 and HL 60 cells. Luminescence 24, 171\u2013177. https:\/\/doi.org\/10.1002\/bio.1091 (2009).","journal-title":"Luminescence"},{"key":"61614_CR58","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1038\/nm1441","volume":"12","author":"CW Wong","year":"2006","unstructured":"Wong, C. W. et al. Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Nat. Med. 12, 950\u2013954. https:\/\/doi.org\/10.1038\/nm1441 (2006).","journal-title":"Nat. Med."},{"key":"61614_CR59","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/cvr\/cvu063","volume":"102","author":"S Morel","year":"2014","unstructured":"Morel, S. et al. Endothelial Cx40 limits myocardial ischaemia\/reperfusion injury in mice. Cardiovasc. Res. 102, 329\u2013337. https:\/\/doi.org\/10.1093\/cvr\/cvu063 (2014).","journal-title":"Cardiovasc. Res."},{"key":"61614_CR60","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/cvr\/cvw004","volume":"109","author":"S Morel","year":"2016","unstructured":"Morel, S. et al. Sphingosine-1-phosphate reduces ischaemia-reperfusion injury by phosphorylating the gap junction protein Connexin43. Cardiovasc. Res. 109, 385\u2013396. https:\/\/doi.org\/10.1093\/cvr\/cvw004 (2016).","journal-title":"Cardiovasc. Res."},{"key":"61614_CR61","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235\u2013242. https:\/\/doi.org\/10.1093\/nar\/28.1.235 (2000).","journal-title":"Nucleic Acids Res."},{"key":"61614_CR62","doi-asserted-by":"publisher","first-page":"W449","DOI":"10.1093\/nar\/gkw329","volume":"44","author":"A Lamiable","year":"2016","unstructured":"Lamiable, A. et al. PEP-FOLD3: faster de novo structure prediction for linear peptides in solution and in complex. Nucleic Acids Res. 44, W449\u2013454. https:\/\/doi.org\/10.1093\/nar\/gkw329 (2016).","journal-title":"Nucleic Acids Res."},{"key":"61614_CR63","doi-asserted-by":"publisher","first-page":"4745","DOI":"10.1021\/ct500592m","volume":"10","author":"Y Shen","year":"2014","unstructured":"Shen, Y., Maupetit, J., Derreumaux, P., Tuffery, P. & Improved PEP-FOLD Approach for Peptide and Miniprotein Structure Prediction. J. Chem. Theory Comput. 10, 4745\u20134758. https:\/\/doi.org\/10.1021\/ct500592m (2014).","journal-title":"J. Chem. Theory Comput."},{"key":"61614_CR64","doi-asserted-by":"publisher","first-page":"W288","DOI":"10.1093\/nar\/gks419","volume":"40","author":"P Thevenet","year":"2012","unstructured":"Thevenet, P. et al. PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 40, W288\u2013293. https:\/\/doi.org\/10.1093\/nar\/gks419 (2012).","journal-title":"Nucleic Acids Res."},{"key":"61614_CR65","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1093\/bioinformatics\/btt262","volume":"29","author":"B Jimenez-Garcia","year":"2013","unstructured":"Jimenez-Garcia, B., Pons, C. & Fernandez-Recio, J. pyDockWEB: a web server for rigid-body protein-protein docking using electrostatics and desolvation scoring. Bioinformatics 29, 1698\u20131699. https:\/\/doi.org\/10.1093\/bioinformatics\/btt262 (2013).","journal-title":"Bioinformatics"},{"key":"61614_CR66","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1093\/bioinformatics\/btu426","volume":"30","author":"E Krieger","year":"2014","unstructured":"Krieger, E. & Vriend, G. YASARA View - molecular graphics for all devices - from smartphones to workstations. Bioinformatics 30, 2981\u20132982. https:\/\/doi.org\/10.1093\/bioinformatics\/btu426 (2014).","journal-title":"Bioinformatics"},{"key":"61614_CR67","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","volume":"61","author":"J Eberhardt","year":"2021","unstructured":"Eberhardt, J., Santos-Martins, D., Tillack, A. F. & Forli, S. AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. J. Chem. Inf. Model. 61, 3891\u20133898. https:\/\/doi.org\/10.1021\/acs.jcim.1c00203 (2021).","journal-title":"J. Chem. Inf. Model."},{"key":"61614_CR68","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1002\/jcc.23899","volume":"36","author":"E Krieger","year":"2015","unstructured":"Krieger, E. & Vriend, G. New ways to boost molecular dynamics simulations. J. Comput. Chem. 36, 996\u20131007. https:\/\/doi.org\/10.1002\/jcc.23899 (2015).","journal-title":"J. Comput. Chem."},{"key":"61614_CR69","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926\u2013935. https:\/\/doi.org\/10.1063\/1.445869 (1983).","journal-title":"J. Chem. Phys."},{"key":"61614_CR70","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1002\/jcc.21787","volume":"32","author":"N Michaud-Agrawal","year":"2011","unstructured":"Michaud-Agrawal, N., Denning, E. J., Woolf, T. B. & Beckstein, O. MDAnalysis: a toolkit for the analysis of molecular dynamics simulations. J. Comput. Chem. 32, 2319\u20132327. https:\/\/doi.org\/10.1002\/jcc.21787 (2011).","journal-title":"J. Comput. Chem."},{"key":"61614_CR71","doi-asserted-by":"publisher","unstructured":"Bouysset, C. & Fiorucci, S. ProLIF: a library to encode molecular interactions as fingerprints. J. Cheminform. 13 https:\/\/doi.org\/10.1186\/s13321-021-00548-6 (2021).","DOI":"10.1186\/s13321-021-00548-6"},{"key":"61614_CR72","doi-asserted-by":"crossref","unstructured":"Gowers, R. J. L. et al. O. MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations. PROC. OF THE 15th PYTHON IN SCIENCE CONF. (2016).","DOI":"10.25080\/Majora-629e541a-00e"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-61614-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-61614-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-61614-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:02:44Z","timestamp":1791889364000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-61614-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["61614"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-61614-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]},"assertion":[{"value":"5 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"31941"}}