{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:23:02Z","timestamp":1760239382795,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation (NRF) of Korea","award":["NRF- 2018R1D1A1B0704984013","NRF-2020R1F1A107578211"],"award-info":[{"award-number":["NRF- 2018R1D1A1B0704984013","NRF-2020R1F1A107578211"]}]},{"name":"GRRC program of Gyeonggi province","award":["GRRC-CHA2017-A02","GRRC-CHA2017-B02"],"award-info":[{"award-number":["GRRC-CHA2017-A02","GRRC-CHA2017-B02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pyrimidine is a privileged scaffold in many synthetic compounds exhibiting diverse pharmacological activities, and is used for therapeutic applications in a broad spectrum of human diseases. In this study, we prepared a small set of pyrimidine libraries based on the structure of two hit compounds that were identified through the screening of an in-house library in order to identify an inhibitor of anoctamin 1 (ANO1). ANO1 is amplified in various types of human malignant tumors, such as head and neck, parathyroid, and gastrointestinal stromal tumors, as well as in breast, lung, and prostate cancers. After initial screening and further structure optimization, we identified Aa3 as a dose-dependent ANO1 blocker. This compound exhibited more potent anti-cancer activity in the NCI-H460 cell line, expressing high levels of ANO1 compared with that in A549 cells that express low levels of ANO1. Our results open a new direction for the development of small-molecule ANO1 blockers composed of a pyrimidine scaffold and a nitrogen-containing heterocyclic moiety, with drug-like properties.<\/jats:p>","DOI":"10.3390\/molecules25215180","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T20:23:35Z","timestamp":1604867015000},"page":"5180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Design of Anticancer 2,4-Diaminopyrimidines as Novel Anoctamin 1 (ANO1) Ion Channel Blockers"],"prefix":"10.3390","volume":"25","author":[{"given":"Taewoo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sinyoung","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haejun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joonseong","family":"Hur","sequence":"additional","affiliation":[{"name":"Natural Products Research Institute, Korea Institute of Science and Technology (KIST), 679 Saimdang-ro, Gangneung 25451, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haedong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seongho","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Duk","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-751X","authenticated-orcid":false,"given":"Seok-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, 120 Haeryong-ro, Pocheon 11160, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ejmech.2016.09.023","article-title":"Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities","volume":"125","author":"Akhtar","year":"2017","journal-title":"Eur. 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