{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:20:49Z","timestamp":1784733649405,"version":"3.55.0"},"reference-count":47,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2018,10]]},"DOI":"10.1124\/jpet.118.248088","type":"journal-article","created":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T12:25:21Z","timestamp":1533299121000},"page":"108-118","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"title":["Ref-1\/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization"],"prefix":"10.1016","volume":"367","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8974-7562","authenticated-orcid":false,"given":"Sheik Pran Babu","family":"Sardar Pasha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1525-0155","authenticated-orcid":false,"given":"Kamakshi","family":"Sishtla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania S.","family":"Sulaiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1440-7066","authenticated-orcid":false,"given":"Bomina","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trupti","family":"Shetty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenil","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9436-6382","authenticated-orcid":false,"given":"Melissa L.","family":"Fishel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2823-7854","authenticated-orcid":false,"given":"James H.","family":"Wikel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9472-1826","authenticated-orcid":false,"given":"Mark R.","family":"Kelley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1402-7875","authenticated-orcid":false,"given":"Timothy W.","family":"Corson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.118.248088_bib1","doi-asserted-by":"crossref","first-page":"e95694","DOI":"10.1371\/journal.pone.0095694","article-title":"Synthesis and mechanistic studies of a novel homoisoflavanone inhibitor of endothelial cell growth","volume":"9","author":"Basavarajappa","year":"2014","journal-title":"PLoS One"},{"key":"10.1124\/jpet.118.248088_bib2","doi-asserted-by":"crossref","first-page":"786","DOI":"10.15252\/emmm.201606561","article-title":"Ferrochelatase is a therapeutic target for ocular neovascularization","volume":"9","author":"Basavarajappa","year":"2017","journal-title":"EMBO Mol Med"},{"key":"10.1124\/jpet.118.248088_bib3","doi-asserted-by":"crossref","first-page":"C296","DOI":"10.1152\/ajpcell.00022.2015","article-title":"Endothelial cell tumor growth is Ape\/ref-1 dependent","volume":"309","author":"Biswas","year":"2015","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1124\/jpet.118.248088_bib4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00109-013-0993-5","article-title":"Ocular neovascularization","volume":"91","author":"Campochiaro","year":"2013","journal-title":"J Mol Med (Berl)"},{"key":"10.1124\/jpet.118.248088_bib5","doi-asserted-by":"crossref","first-page":"e47462","DOI":"10.1371\/journal.pone.0047462","article-title":"APE1\/Ref-1 regulates STAT3 transcriptional activity and APE1\/Ref-1-STAT3 dual-targeting effectively inhibits pancreatic cancer cell survival","volume":"7","author":"Cardoso","year":"2012","journal-title":"PLoS One"},{"key":"10.1124\/jpet.118.248088_bib6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/sj.cdd.4400639","article-title":"Evidence that the bifunctional redox factor \/ AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina","volume":"7","author":"Chiarini","year":"2000","journal-title":"Cell Death Differ"},{"key":"10.1124\/jpet.118.248088_bib7","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ajo.2011.01.053","article-title":"Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration","volume":"152","author":"Day","year":"2011","journal-title":"Am J Ophthalmol"},{"key":"10.1124\/jpet.118.248088_bib8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0921-8777(00)00046-X","article-title":"Going APE over ref-1","volume":"461","author":"Evans","year":"2000","journal-title":"Mutat Res"},{"key":"10.1124\/jpet.118.248088_bib9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/eye.2013.107","article-title":"Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature","volume":"27","author":"Falavarjani","year":"2013","journal-title":"Eye (Lond)"},{"key":"10.1124\/jpet.118.248088_bib10","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.exphem.2010.08.011","article-title":"Inhibition of the redox function of APE1\/Ref-1 in myeloid leukemia cell lines results in a hypersensitive response to retinoic acid-induced differentiation and apoptosis","volume":"38","author":"Fishel","year":"2010","journal-title":"Exp Hematol"},{"key":"10.1124\/jpet.118.248088_bib11","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1158\/1535-7163.MCT-11-0107","article-title":"Impact of APE1\/Ref-1 redox inhibition on pancreatic tumor growth","volume":"10","author":"Fishel","year":"2011","journal-title":"Mol Cancer Ther"},{"key":"10.1124\/jpet.118.248088_bib12","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1074\/jbc.M114.621995","article-title":"Apurinic\/apyrimidinic endonuclease\/redox factor-1 (APE1\/Ref-1) redox function negatively regulates NRF2","volume":"290","author":"Fishel","year":"2015","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248088_bib13","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1128\/MCB.16.9.4604","article-title":"Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1","volume":"16","author":"Forsythe","year":"1996","journal-title":"Mol Cell Biol"},{"key":"10.1124\/jpet.118.248088_bib14","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.preteyeres.2010.05.003","article-title":"Animal models of choroidal and retinal neovascularization","volume":"29","author":"Grossniklaus","year":"2010","journal-title":"Prog Retin Eye Res"},{"key":"10.1124\/jpet.118.248088_bib15","first-page":"379","article-title":"Apurinic\/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages","volume":"31","author":"Jedinak","year":"2011","journal-title":"Anticancer Res"},{"key":"10.1124\/jpet.118.248088_bib16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.visres.2010.10.008","article-title":"Inhibition of APE1\/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo","volume":"51","author":"Jiang","year":"2011","journal-title":"Vision Res"},{"key":"10.1124\/jpet.118.248088_bib17","series-title":"The Tumor Microenvironment","first-page":"133","article-title":"DNA repair & redox signaling","author":"Kelley","year":"2010"},{"key":"10.1124\/jpet.118.248088_bib18","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/1874467211205010036","article-title":"APE1\/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair\/redox protein APE1\/Ref-1","volume":"5","author":"Kelley","year":"2012","journal-title":"Curr Mol Pharmacol"},{"key":"10.1124\/jpet.118.248088_bib19","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1089\/ars.2010.3410","article-title":"Functional analysis of novel analogues of E3330 that block the redox signaling activity of the multifunctional AP endonuclease\/redox signaling enzyme APE1\/Ref-1","volume":"14","author":"Kelley","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"10.1124\/jpet.118.248088_bib20","unstructured":"Kelley MR and Wikel JH (2015) inventors, Indiana University Research and Technology Corporation, ApeX Therapeutics, Inc., assignees. Quinone compounds for treating Ape1 mediated diseases. U.S. patent 9,193,700. 2015 Nov 24."},{"key":"10.1124\/jpet.118.248088_bib21","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1124\/jpet.116.235283","article-title":"Identification and characterization of new chemical entities targeting apurinic\/apyrimidinic endonuclease 1 for the prevention of chemotherapy-induced peripheral neuropathy","volume":"359","author":"Kelley","year":"2016","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.118.248088_bib22","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1074\/jbc.275.7.4618","article-title":"A redox mechanism controls differential DNA binding activities of hypoxia-inducible factor (HIF) 1alpha and the HIF-like factor","volume":"275","author":"Lando","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248088_bib23","doi-asserted-by":"crossref","first-page":"8222","DOI":"10.1158\/0008-5472.CAN-10-0894","article-title":"Modulation of gene expression and tumor cell growth by redox modification of STAT3","volume":"70","author":"Li","year":"2010","journal-title":"Cancer Res"},{"key":"10.1124\/jpet.118.248088_bib24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.redox.2014.01.023","article-title":"Inhibition of APE1\/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization","volume":"2","author":"Li","year":"2014","journal-title":"Redox Biol"},{"key":"10.1124\/jpet.118.248088_bib25","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1167\/iovs.14-14451","article-title":"Suppression of choroidal neovascularization through inhibition of APE1\/Ref-1 redox activity","volume":"55","author":"Li","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1124\/jpet.118.248088_bib26","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1158\/1535-7163.MCT-16-0253","article-title":"Regulation of HIF1\u03b1 under hypoxia by APE1\/Ref-1 impacts CA9 expression: dual targeting in patient-derived 3D pancreatic cancer models","volume":"15","author":"Logsdon","year":"2016","journal-title":"Mol Cancer Ther"},{"key":"10.1124\/jpet.118.248088_bib27","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.3892\/ol.2014.1864","article-title":"Aberrant expression of redox protein Ape1 in colon cancer stem cells","volume":"7","author":"Lou","year":"2014","journal-title":"Oncol Lett"},{"key":"10.1124\/jpet.118.248088_bib28","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1089\/ars.2008.2120","article-title":"Role of the multifunctional DNA repair and redox signaling protein Ape1\/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1","volume":"10","author":"Luo","year":"2008","journal-title":"Antioxid Redox Signal"},{"key":"10.1124\/jpet.118.248088_bib29","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1021\/bi201034z","article-title":"Characterization of the redox activity and disulfide bond formation in apurinic\/apyrimidinic endonuclease","volume":"51","author":"Luo","year":"2012","journal-title":"Biochemistry"},{"key":"10.1124\/jpet.118.248088_bib30","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/bjo.2006.113902","article-title":"Non-responders to bevacizumab (Avastin) therapy of choroidal neovascular lesions","volume":"91","author":"Lux","year":"2007","journal-title":"Br J Ophthalmol"},{"key":"10.1124\/jpet.118.248088_bib31","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.18632\/oncotarget.23493","article-title":"APE1\/Ref-1 redox-specific inhibition decreases survivin protein levels and induces cell cycle arrest in prostate cancer cells","volume":"9","author":"McIlwain","year":"2017","journal-title":"Oncotarget"},{"key":"10.1124\/jpet.118.248088_bib32","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1158\/1541-7786.MCR-06-0329","article-title":"A dominant-negative form of the major human abasic endonuclease enhances cellular sensitivity to laboratory and clinical DNA-damaging agents","volume":"5","author":"McNeill","year":"2007","journal-title":"Mol Cancer Res"},{"key":"10.1124\/jpet.118.248088_bib33","doi-asserted-by":"crossref","first-page":"44548","DOI":"10.1074\/jbc.M202970200","article-title":"Spatial redox regulation of a critical cysteine residue of NF-kappa B in vivo","volume":"277","author":"Nishi","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.118.248088_bib34","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1167\/iovs.14-15067","article-title":"Reliability of the mouse model of choroidal neovascularization induced by laser photocoagulation","volume":"55","author":"Poor","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"10.1124\/jpet.118.248088_bib35","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.maturitas.2010.02.006","article-title":"Age-related macular degeneration: current and novel therapies","volume":"66","author":"Prasad","year":"2010","journal-title":"Maturitas"},{"key":"10.1124\/jpet.118.248088_bib36","doi-asserted-by":"crossref","first-page":"14548","DOI":"10.1073\/pnas.212319799","article-title":"Selenomethionine regulation of p53 by a ref1-dependent redox mechanism","volume":"99","author":"Seo","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/jpet.118.248088_bib37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41698-017-0023-0","article-title":"Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic","volume":"1","author":"Shah","year":"2017","journal-title":"NPJ Precis Oncol"},{"key":"10.1124\/jpet.118.248088_bib38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1021\/bi101248s","article-title":"Interactions of apurinic\/apyrimidinic endonuclease with a redox inhibitor: evidence for an alternate conformation of the enzyme","volume":"50","author":"Su","year":"2011","journal-title":"Biochemistry"},{"key":"10.1124\/jpet.118.248088_bib39","doi-asserted-by":"crossref","first-page":"25509","DOI":"10.1038\/srep25509","article-title":"A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy","volume":"6","author":"Sulaiman","year":"2016","journal-title":"Sci Rep"},{"key":"10.1124\/jpet.118.248088_bib40","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1089\/jop.2015.0049","article-title":"A simple optical coherence tomography quantification method for choroidal neovascularization","volume":"31","author":"Sulaiman","year":"2015","journal-title":"J Ocul Pharmacol Ther"},{"key":"10.1124\/jpet.118.248088_bib41","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/j.dnarep.2011.06.004","article-title":"The repair function of the multifunctional DNA repair\/redox protein APE1 is neuroprotective after ionizing radiation","volume":"10","author":"Vasko","year":"2011","journal-title":"DNA Repair (Amst)"},{"key":"10.1124\/jpet.118.248088_bib42","first-page":"515","article-title":"Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma","volume":"21","author":"Wenzel","year":"2015","journal-title":"Mol Vis"},{"key":"10.1124\/jpet.118.248088_bib43","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/j.1460-2075.1992.tb05097.x","article-title":"Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity","volume":"11","author":"Xanthoudakis","year":"1992","journal-title":"EMBO J"},{"key":"10.1124\/jpet.118.248088_bib44","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1002\/j.1460-2075.1992.tb05411.x","article-title":"Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme","volume":"11","author":"Xanthoudakis","year":"1992","journal-title":"EMBO J"},{"key":"10.1124\/jpet.118.248088_bib45","doi-asserted-by":"crossref","first-page":"453","DOI":"10.14336\/AD.2017.1130","article-title":"APX3330 promotes neurorestorative effects after stroke in type one diabetic rats","volume":"9","author":"Yan","year":"2018","journal-title":"Aging Dis"},{"key":"10.1124\/jpet.118.248088_bib46","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1021\/bi400179m","article-title":"Inhibition of apurinic\/apyrimidinic endonuclease I\u2019s redox activity revisited","volume":"52","author":"Zhang","year":"2013","journal-title":"Biochemistry"},{"key":"10.1124\/jpet.118.248088_bib47","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1002\/jcp.21666","article-title":"The Ape-1\/Ref-1 redox antagonist E3330 inhibits the growth of tumor endothelium and endothelial progenitor cells: therapeutic implications in tumor angiogenesis","volume":"219","author":"Zou","year":"2009","journal-title":"J Cell Physiol"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524266878?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524266878?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.118.248088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T15:00:44Z","timestamp":1739977244000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524266878"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["S0022356524266878"],"URL":"https:\/\/doi.org\/10.1124\/jpet.118.248088","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/296590","asserted-by":"object"}]},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2018,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ref-1\/APE1 Inhibition with Novel Small Molecules Blocks Ocular Neovascularization","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.118.248088","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}