{"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":1783490392526,"version":"3.55.0"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018R1A6A1A03023718"],"award-info":[{"award-number":["NRF-2018R1A6A1A03023718"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1C1C1008332"],"award-info":[{"award-number":["NRF-2020R1C1C1008332"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1I1A1A01047951"],"award-info":[{"award-number":["NRF-2021R1I1A1A01047951"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis transmembrane conductance regulator (CFTR) is highly expressed on the ocular epithelium and plays a pivotal role in the fluid secretion driven by chloride transport. Dry eye disease is one of the most common diseases with limited therapeutic options. In this study, a high-throughput screening was performed to identify novel CFTR activators capable of inducing chloride secretion on the ocular surface. The screening of 50,000 small molecules revealed three novel CFTR activators. Among them, the most potent CFTR activator, Cact-3 (7-(3,4-dimethoxyphenyl)-N-(4-ethoxyphenyl)pyrazolo [1,5-\u03b1]pyrimidine-2-carboxamide), produced large and sustained Cl\u2212 currents in WT-CFTR-expressing FRT cells with no alterations of ANO1 and hERG channel activity. The application of Cact-3 strongly activated CFTR in the ocular epithelia of mice and it also significantly increased CFTR-mediated Cl\u2212 transport in a primary cultured human conjunctival epithelium. Cact-3 strongly stimulated tear secretion in normal mice. In addition, Cact-3 significantly reduced ocular surface damage and the expression of proinflammatory factors, including interleukin (IL)-1\u03b2, IL-6, tumor necrosis factor (TNF)-\u03b1, and interferon (IFN)-\u03b3 in an experimental mouse model of dry eye disease. These results suggest that Cact-3, a novel CFTR activator, may be a potential development candidate for the treatment of dry eye disease.<\/jats:p>","DOI":"10.3390\/ijms23095206","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T14:49:38Z","timestamp":1651848578000},"page":"5206","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel CFTR Activator Cact-3 Ameliorates Ocular Surface Dysfunctions in Scopolamine-Induced Dry Eye Mice"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1339-6388","authenticated-orcid":false,"given":"Dongkyu","family":"Jeon","sequence":"first","affiliation":[{"name":"Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2160-1679","authenticated-orcid":false,"given":"Ikhyun","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-3217","authenticated-orcid":false,"given":"Ho K.","family":"Lee","sequence":"additional","affiliation":[{"name":"Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Rahm","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunhi","family":"Ryu","sequence":"additional","affiliation":[{"name":"Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchul","family":"Yoon","sequence":"additional","affiliation":[{"name":"Research Laboratories, ILDONG Pharmaceutical Co., Ltd., 20, Samsung 1-ro 1-gil, Hwaseong 18449, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-im","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1480-7433","authenticated-orcid":false,"given":"Wan","family":"Namkung","sequence":"additional","affiliation":[{"name":"Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Korea"},{"name":"Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemoon-Gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajo.2006.11.060","article-title":"Impact of dry eye syndrome on vision-related quality of life","volume":"143","author":"Miljanovic","year":"2007","journal-title":"Am. 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