{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:59:52Z","timestamp":1783490392532,"version":"3.55.0"},"reference-count":27,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ocular Pharmacology and Therapeutics"],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose:<\/jats:title>\n                    <jats:p>\n                      Dry eye disorders are a major health care burden. We previously reported the identification of\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -methyl-\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -phenyl-6-(2,2,3,3-tetrafluoropropoxy)-1,3,5-triazine-2,4-diamine [cystic fibrosis transmembrane conductance regulator (CFTR)\n                      <jats:sub>act<\/jats:sub>\n                      -K267], which activated human wild-type CFTR chloride conductance with EC\n                      <jats:sub>50<\/jats:sub>\n                      \u223c 30\u2009nM. Here, we report\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evidence for CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267 efficacy in an experimental mouse model of dry eye using a human compatible ophthalmic vehicle.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      CFTR activation in mice\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      was demonstrated by ocular surface potential difference (OSPD) measurements. Ocular surface pharmacodynamics was measured in tear fluid samples obtained at different times after topical administration of CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267. Dry eye was produced by lacrimal duct cautery (LDC) and corneal epithelial injury and was assessed by Lissamine green (LG) staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      OSPD measurements demonstrated a hyperpolarization of \u22128.6\u2009\u00b1\u20093\u2009mV (standard error of the mean, 5 mice) in response to CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267 exposure in low chloride solution that was reversed by a CFTR inhibitor. Following single-dose topical administration of 2\u2009nmol CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267, tear fluid CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267 concentration was &gt;500\u2009nM for more than 6\u2009h. Following LDC, corneal surface epithelial injury, as assessed by LG staining, was substantially reversed in 10 of 12 eyes receiving 2\u2009nmol CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267 3 times daily starting on day 2, when marked epithelial injury had already occurred. Improvement was seen in 3 of 12 vehicle-treated eyes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      These studies provide\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evidence in mice for the efficacy of a topical, human use compatible CFTR\n                      <jats:sub>act<\/jats:sub>\n                      -K267 formulation in stimulating chloride secretion and reversing corneal epithelial injury in dry eye.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2019.0087","type":"journal-article","created":{"date-parts":[[2020,1,14]],"date-time":"2020-01-14T11:36:33Z","timestamp":1579001793000},"page":"147-153","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Nanomolar Potency Aminophenyltriazine CFTR Activator Reverses Corneal Epithelial Injury in a Mouse Model of Dry Eye"],"prefix":"10.1177","volume":"36","author":[{"given":"Xiaolan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medicine and Physiology and University of California, San Francisco, California."},{"name":"Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine and Physiology and University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine and Physiology and University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianying","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Physiology and University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neel D.","family":"Pasricha","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie M.","family":"Schallhorn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc H.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Palo Alto Medical Foundation, Palo Alto, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vuk","family":"Koprivica","sequence":"additional","affiliation":[{"name":"Vanda Pharmaceuticals, Inc., Washington, District of Columbia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Verkman","sequence":"additional","affiliation":[{"name":"Department of Medicine and Physiology and University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2019.01.026"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S188314"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.04.017"},{"key":"e_1_3_5_5_2","first-page":"CD009729","article-title":"Over the counter (OTC) artificial tear drops for dry eye syndrome","volume":"2","author":"Pucker A.D.","year":"2016","unstructured":"Pucker A.D., , Ng S.M., , and Nichols J.J. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst. Rev. 2:CD009729, 2016.","journal-title":"Cochrane Database Syst. Rev"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000001734"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0000000000000657"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22533"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e3182254b42"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-1314"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500180"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.6b01792"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22525"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000000264"},{"key":"e_1_3_5_15_2","first-page":"1261","article-title":"Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency?","volume":"40","author":"Sullivan D.A.","year":"1999","unstructured":"Sullivan D.A., , Krenzer K.L., , Sullivan B.D., , Tolls D.B., , Toda I., , and Dana M.R. Does androgen insufficiency cause lacrimal gland inflammation and aqueous tear deficiency?. Invest. Ophthalmol. Vis. Sci. 40:1261\u20131265, 1999.","journal-title":"Invest. Ophthalmol. Vis. Sci"},{"key":"e_1_3_5_16_2","first-page":"1957","article-title":"Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease","volume":"19","author":"Vijmasi T.","year":"2013","unstructured":"Vijmasi T., , Chen F.Y., , Chen Y.T., , Gallup M., , and McNamara N. Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease. Mol. Vis. 19:1957\u20131965, 2013.","journal-title":"Mol. Vis"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.03.013"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-005-0059-2"},{"key":"e_1_3_5_19_2","first-page":"469","article-title":"Establishment of a continuous untransfected human corneal endothelial cell line and its biocompatibility to denuded amniotic membrane","volume":"17","author":"Fan T.","year":"2011","unstructured":"Fan T., , Zhao J., , Ma X., , Xu X., , Zhao W., , and Xu B. Establishment of a continuous untransfected human corneal endothelial cell line and its biocompatibility to denuded amniotic membrane. Mol. Vis. 17:469\u2013480, 2011.","journal-title":"Mol. Vis"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00384.2001"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00201.2004"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1022514031645"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.24.3.182.8297"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1139\/y02-066"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.006"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2017.05.008"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S69486"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2019.02.006"}],"container-title":["Journal of Ocular Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/jop.2019.0087","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2019.0087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/jop.2019.0087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T14:43:34Z","timestamp":1777646614000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/jop.2019.0087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,1]]},"references-count":27,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,4,1]]}},"alternative-id":["10.1089\/jop.2019.0087"],"URL":"https:\/\/doi.org\/10.1089\/jop.2019.0087","relation":{},"ISSN":["1080-7683","1557-7732"],"issn-type":[{"value":"1080-7683","type":"print"},{"value":"1557-7732","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,1]]}}}