{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:19:24Z","timestamp":1790421564042,"version":"4.1.0"},"reference-count":43,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2019,3]]},"DOI":"10.1016\/j.phrs.2019.01.011","type":"journal-article","created":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T05:06:18Z","timestamp":1546751178000},"page":"319-330","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Inhibition of Eph\/ephrin interaction with the small molecule UniPR500 improves glucose tolerance in healthy and insulin-resistant mice"],"prefix":"10.1016","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6414-8221","authenticated-orcid":false,"given":"C.","family":"Giorgio","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-8765","authenticated-orcid":false,"given":"M.","family":"Incerti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Pala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Chiodelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-5908","authenticated-orcid":false,"given":"M.","family":"Rusnati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M.","family":"Cantoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-4733","authenticated-orcid":false,"given":"R.","family":"Di Lecce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Barocelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-1306","authenticated-orcid":false,"given":"S.","family":"Bertoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0393-9262","authenticated-orcid":false,"given":"P.","family":"Ravassard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Manenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-2198","authenticated-orcid":false,"given":"L.","family":"Piemonti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1061-1991","authenticated-orcid":false,"given":"F.","family":"Ferlenghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lodola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tognolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.phrs.2019.01.011_bib0005","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.bbrc.2006.02.003","article-title":"MIN6 beta-cell-beta-cell interactions influence insulin secretory responses to nutrients and non-nutrients","volume":"343","author":"Luther","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.phrs.2019.01.011_bib0010","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.cell.2007.02.044","article-title":"EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from pancreatic islets","volume":"129","author":"Konstantinova","year":"2007","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2019.01.011_bib0015","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cell.2008.03.011","article-title":"Eph-ephrin bidirectional signaling in physiology and disease","volume":"133","author":"Pasquale","year":"2008","journal-title":"Cell"},{"key":"10.1016\/j.phrs.2019.01.011_bib0020","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1038\/21907","article-title":"Eph receptors and ephrins restrict cell intermingling and communication","volume":"400","author":"Mellitzer","year":"1999","journal-title":"Nature"},{"key":"10.1016\/j.phrs.2019.01.011_bib0025","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1007\/s00125-011-2283-5","article-title":"Transcriptomes of the major human pancreatic cell types","volume":"54","author":"Dorrell","year":"2011","journal-title":"Diabetologia"},{"key":"10.1016\/j.phrs.2019.01.011_bib0030","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1007\/s00125-013-2877-1","article-title":"Pharmacological inhibition of Eph receptors enhances glucose-stimulated insulin secretion from mouse and human pancreatic islets","volume":"56","author":"Jain","year":"2013","journal-title":"Diabetologia"},{"key":"10.1016\/j.phrs.2019.01.011_bib0035","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ejmech.2017.07.029","article-title":"Targeting Eph\/ephrin system in cancer therapy","volume":"142","author":"Lodola","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.phrs.2019.01.011_bib0040","doi-asserted-by":"crossref","first-page":"5195","DOI":"10.1111\/bph.12669","article-title":"UniPR129 is a competitive small molecule Eph-ephrin antagonist blocking in vitro angiogenesis at low micromolar concentrations","volume":"171","author":"Hassan-Mohamed","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.phrs.2019.01.011_bib0045","first-page":"8048","article-title":"Exploiting free-energy minima to design novel EphA2 protein-Protein antagonists: from simulation to experiment and return","volume":"22","author":"Russo","year":"2016","journal-title":"Chem. Weinh. Bergstr. Ger."},{"key":"10.1016\/j.phrs.2019.01.011_bib0050","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/cmdc.201300305","article-title":"Target hopping as a useful tool for the identification of novel EphA2 protein-protein antagonists","volume":"9","author":"Tognolini","year":"2014","journal-title":"ChemMedChem."},{"key":"10.1016\/j.phrs.2019.01.011_bib0055","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.ejmech.2015.08.048","article-title":"\u0394(5)-Cholenoyl-amino acids as selective and orally available antagonists of the Eph-ephrin system","volume":"103","author":"Castelli","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.phrs.2019.01.011_bib0060","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1172\/JCI58447","article-title":"A genetically engineered human pancreatic \u03b2 cell line exhibiting glucose-inducible insulin secretion","volume":"121","author":"Ravassard","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.phrs.2019.01.011_bib0065","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0042115","article-title":"Oleanolic acid reduces hyperglycemia beyond treatment period with Akt\/FoxO1-induced suppression of hepatic gluconeogenesis in type-2 diabetic mice","volume":"7","author":"Zeng","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.phrs.2019.01.011_bib0070","doi-asserted-by":"crossref","DOI":"10.1155\/2011\/416254","article-title":"Development of a nongenetic mouse model of type 2 diabetes","volume":"2011","author":"Gilbert","year":"2011","journal-title":"Exp. Diabetes Res."},{"key":"10.1016\/j.phrs.2019.01.011_bib0075","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1476-5381.1959.tb00928.x","article-title":"Some quantitative uses of drug antagonists","volume":"14","author":"Arunlakshana","year":"1959","journal-title":"Br. J. Pharmacol. Chemother."},{"key":"10.1016\/j.phrs.2019.01.011_bib0080","first-page":"13043","article-title":"Synthesis and structure-activity relationships of amino acid conjugates of cholanic acid as antagonists of the EphA2 receptor","volume":"18","author":"Russo","year":"2013","journal-title":"Mol. Basel Switz."},{"key":"10.1016\/j.phrs.2019.01.011_bib0085","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.cmet.2009.08.001","article-title":"TGR5-mediated bile acid sensing controls glucose homeostasis","volume":"10","author":"Thomas","year":"2009","journal-title":"Cell Metab."},{"key":"10.1016\/j.phrs.2019.01.011_bib0090","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1021\/ml400247k","article-title":"Probing the binding site of bile acids in TGR5","volume":"4","author":"Macchiarulo","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.phrs.2019.01.011_bib0095","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1021\/acs.jmedchem.6b01642","article-title":"Metadynamics for perspective drug design: computationally driven synthesis of new protein-Protein interaction inhibitors targeting the EphA2 receptor","volume":"60","author":"Incerti","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.phrs.2019.01.011_bib0100","first-page":"302","article-title":"The bile acid TGR5 membrane receptor: from basic research to clinical application","volume":"46","author":"Duboc","year":"2014","journal-title":"Dig. Liver Dis. Off. J. Ital. Soc. Gastroenterol. Ital. Assoc. Study Liver."},{"key":"10.1016\/j.phrs.2019.01.011_bib0105","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.molmet.2017.12.007","article-title":"The EndoC-\u03b2H1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates","volume":"8","author":"Tsonkova","year":"2018","journal-title":"Mol. Metab."},{"key":"10.1016\/j.phrs.2019.01.011_bib0110","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/B978-0-12-407766-9.00017-1","article-title":"Protein tyrosine phosphatase 1B (PTP1B) and obesity","volume":"91","author":"Cho","year":"2013","journal-title":"Vitam. Horm."},{"key":"10.1016\/j.phrs.2019.01.011_bib0115","doi-asserted-by":"crossref","first-page":"7237","DOI":"10.1016\/j.bmcl.2012.09.040","article-title":"Synthesis and biological evaluation of 4,4-dimethyl lithocholic acid derivatives as novel inhibitors of protein tyrosine phosphatase 1B","volume":"22","author":"He","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.phrs.2019.01.011_bib0120","series-title":"Drug- Prop. Concepts Struct. Des. Methods","first-page":"43","article-title":"Lipophilicity","author":"Kerns","year":"2008"},{"key":"10.1016\/j.phrs.2019.01.011_bib0125","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/978-3-642-14541-4_4","article-title":"Role of the intestinal bile acid transporters in bile acid and drug disposition","author":"Dawson","year":"2011","journal-title":"Handb. Exp. Pharmacol."},{"issue":"Suppl 3","key":"10.1016\/j.phrs.2019.01.011_bib0130","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.2337\/diabetes.53.suppl_3.S215","article-title":"The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes","volume":"53","author":"Winzell","year":"2004","journal-title":"Diabetes"},{"key":"10.1016\/j.phrs.2019.01.011_bib0135","series-title":"Rodent Models of Streptozotocin\u2010induced Diabetic Nephropathy (Methods in Renal Research) - TESCH","year":"2007"},{"key":"10.1016\/j.phrs.2019.01.011_bib0140","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1258\/la.2010.010090","article-title":"Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models","volume":"45","author":"Deeds","year":"2011","journal-title":"Lab. Anim."},{"key":"10.1016\/j.phrs.2019.01.011_bib0145","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1158\/1078-0432.CCR-15-0695","article-title":"Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions","volume":"21","author":"Damelin","year":"2015","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"10.1016\/j.phrs.2019.01.011_bib0150","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10637-012-9801-2","article-title":"Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors","volume":"31","author":"Annunziata","year":"2013","journal-title":"Invest. New Drugs"},{"key":"10.1016\/j.phrs.2019.01.011_bib0155","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/S0959-8049(16)32623-5","article-title":"A first-in-human phase I study of sEphB4-HSA in patients with advanced solid tumors with expansion at the maximum tolerated dose (MTD) or recommended phase II dose (RP2D)","volume":"69","author":"El-Khoueiry","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.phrs.2019.01.011_bib0160","doi-asserted-by":"crossref","first-page":"S126","DOI":"10.1016\/S0959-8049(16)32976-8","article-title":"Circulating tumor cell analysis in a first-in-human phase I study of sEphB4-HSA, an inhibitor of EphrinB2-EphB4 signaling","volume":"69","author":"Hugen","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.phrs.2019.01.011_bib0165","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1021\/acs.jmedchem.7b01837","article-title":"Reduction of circulating Cancer cells and metastases in breast-cancer models by a potent EphA2-Agonistic peptide-drug conjugate","volume":"61","author":"Salem","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.phrs.2019.01.011_bib0170","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.chembiol.2017.01.006","article-title":"Potent and selective EphA4 agonists for the treatment of ALS","volume":"24","author":"Wu","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"10.1016\/j.phrs.2019.01.011_bib0175","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.drudis.2013.11.017","article-title":"Therapeutic perspectives of Eph-ephrin system modulation","volume":"19","author":"Tognolini","year":"2014","journal-title":"Drug Discov. Today."},{"key":"10.1016\/j.phrs.2019.01.011_bib0180","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.molmet.2017.12.007","article-title":"The EndoC-\u03b2H1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates","volume":"8","author":"Tsonkova","year":"2018","journal-title":"Mol. Metab."},{"key":"10.1016\/j.phrs.2019.01.011_bib0185","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/1744666X.2017.1266257","article-title":"C1858T polymorphism of protein tyrosine phosphatase non-receptor Type 22 (PTPN22): an eligible target for prevention of type 1 diabetes?","volume":"13","author":"Prezioso","year":"2017","journal-title":"Expert Rev. Clin. Immunol."},{"key":"10.1016\/j.phrs.2019.01.011_bib0190","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1038\/s41598-018-23026-w","article-title":"A beta-cell protecting drug, reduces type 1 diabetes incidence in NOD mice","volume":"8","author":"Lee","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.phrs.2019.01.011_bib0195","doi-asserted-by":"crossref","first-page":"809","DOI":"10.2337\/db06-0619","article-title":"CCL4 protects from type 1 diabetes by altering islet \u03b2-Cell\u2013targeted inflammatory responses","volume":"56","author":"Meagher","year":"2007","journal-title":"Diabetes"},{"key":"10.1016\/j.phrs.2019.01.011_bib0200","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.3389\/fimmu.2018.01086","article-title":"New horizons in the treatment of type 1 diabetes: more intense immunosuppression and Beta cell replacement","volume":"9","author":"Couri","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.phrs.2019.01.011_bib0205","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4161\/19336918.2014.970028","article-title":"Ephrin-Eph signaling in embryonic tissue separation","volume":"8","author":"Fagotto","year":"2014","journal-title":"Cell Adhes. Migr."},{"key":"10.1016\/j.phrs.2019.01.011_bib0210","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrd4175","article-title":"Therapeutic targeting of EPH receptors and their ligands","volume":"13","author":"Boyd","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.phrs.2019.01.011_bib0215","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/ejp.922","article-title":"Activation of ephrinB-EphB receptor signalling in rat spinal cord contributes to maintenance of diabetic neuropathic pain","volume":"21","author":"Deng","year":"2017","journal-title":"Eur. J. Pain Lond. Engl."}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661818308223?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661818308223?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,2,23]],"date-time":"2019-02-23T11:51:31Z","timestamp":1550922691000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661818308223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":43,"alternative-id":["S1043661818308223"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2019.01.011","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Inhibition of Eph\/ephrin interaction with the small molecule UniPR500 improves glucose tolerance in healthy and insulin-resistant mice","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2019.01.011","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}