{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T02:12:03Z","timestamp":1769307123300,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science Technology, Taiwan","award":["107-2622-B-033-001-CC2"],"award-info":[{"award-number":["107-2622-B-033-001-CC2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Safety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., inducing either tachycardia, bradycardia or arrhythmia. The zebrafish model could be used to screen drug libraries with potential cardiotoxicity in a high-throughput manner. In addition, the fundamental principles of replacement, reduction, and refinement of laboratory animal usage, 3R, could be achieved by using zebrafish as an alternative to animal models. In this study, we used a simple ImageJ-based method to evaluate and screen 70 ion channel ligands and successfully identify six compounds with strong cardiotoxicity in vivo. Next, we conducted an in silico-based molecular docking simulation to elucidate five identified compounds that might interact with domain III or domain IV of the Danio rerio L-type calcium channel (LTCC), a known pharmaceutically important target for arrhythmia. In conclusion, in this study, we provide a web lab and dry lab combinatorial approach to perform in vivo cardiotoxicity drug screening and in silico mechanistic studies.<\/jats:p>","DOI":"10.3390\/cells8060566","type":"journal-article","created":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T03:16:51Z","timestamp":1560136611000},"page":"566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish"],"prefix":"10.3390","volume":"8","author":[{"given":"Bonifasius Putera","family":"Sampurna","sequence":"first","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiorency","family":"Santoso","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Hau","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin-Chung","family":"Wu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Audira","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"},{"name":"Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stevhen","family":"Juniardi","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Ren","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biological Science &amp; Technology College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8096-3402","authenticated-orcid":false,"given":"Ying-Ting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6398-8672","authenticated-orcid":false,"given":"Chung-Der","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"},{"name":"Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan"},{"name":"Center of Nanotechnology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"},{"name":"Center of Biomedical Technology, Chung Yuan Christian University, Chung-Li 32023, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/clpt.2011.9","article-title":"Opportunities for use of human ips cells in predictive toxicology","volume":"89","author":"Anson","year":"2011","journal-title":"Clin. 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