{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:18:48Z","timestamp":1779322728614,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology","award":["MOST 108-2313-B-033-001-MY3"],"award-info":[{"award-number":["MOST 108-2313-B-033-001-MY3"]}]},{"name":"Ministry of Science and Technology","award":["MOST 107-2622-B-033-001-CC2"],"award-info":[{"award-number":["MOST 107-2622-B-033-001-CC2"]}]},{"name":"Ministry of Science and Technology","award":["MOST 110-2314-B-195-008"],"award-info":[{"award-number":["MOST 110-2314-B-195-008"]}]},{"name":"Ministry of Science and Technology","award":["MMH-111-125"],"award-info":[{"award-number":["MMH-111-125"]}]},{"name":"MacKay Memorial Hospital intramural funding","award":["MOST 108-2313-B-033-001-MY3"],"award-info":[{"award-number":["MOST 108-2313-B-033-001-MY3"]}]},{"name":"MacKay Memorial Hospital intramural funding","award":["MOST 107-2622-B-033-001-CC2"],"award-info":[{"award-number":["MOST 107-2622-B-033-001-CC2"]}]},{"name":"MacKay Memorial Hospital intramural funding","award":["MOST 110-2314-B-195-008"],"award-info":[{"award-number":["MOST 110-2314-B-195-008"]}]},{"name":"MacKay Memorial Hospital intramural funding","award":["MMH-111-125"],"award-info":[{"award-number":["MMH-111-125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase in nkx2.5 expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.<\/jats:p>","DOI":"10.3390\/ijms231911711","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T23:39:31Z","timestamp":1665272371000},"page":"11711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Investigating Potential Cardiovascular Toxicity of Two Anti-Leukemia Drugs of Asciminib and Ponatinib in Zebrafish Embryos"],"prefix":"10.3390","volume":"23","author":[{"given":"Huan-Chau","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, Taipei 10449, Taiwan"},{"name":"Laboratory of Good Clinical Research Center, Department of Medical Research, Mackay Memorial Hospital, No. 45, Minsheng Road, Tamsui District, New Taipei City 25160, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5715-9827","authenticated-orcid":false,"given":"Ferry","family":"Saputra","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Audira","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Heng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chinese Culture University, Taipei 11114, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6398-1828","authenticated-orcid":false,"given":"Marri Jmelou M.","family":"Roldan","sequence":"additional","affiliation":[{"name":"The Graduate School, Faculty of Pharmacy, University of Santo Tomas, Manila 1008, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-6763","authenticated-orcid":false,"given":"Honeymae C.","family":"Alos","sequence":"additional","affiliation":[{"name":"The Graduate School, University of Santo Tomas, Manila 1008, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5500-5680","authenticated-orcid":false,"given":"Charlaine A.","family":"Aventurado","sequence":"additional","affiliation":[{"name":"The Graduate School, University of Santo Tomas, Manila 1008, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-9710","authenticated-orcid":false,"given":"Ross D.","family":"Vasquez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila 1008, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guan-Jhe","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2282-0416","authenticated-orcid":false,"given":"Ken-Hong","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, Taipei 10449, Taiwan"},{"name":"Laboratory of Good Clinical Research Center, Department of Medical Research, Mackay Memorial Hospital, No. 45, Minsheng Road, Tamsui District, New Taipei City 25160, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 252, 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 Chemistry, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"},{"name":"Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"},{"name":"Center of Nanotechnology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"},{"name":"Research Center for Aquatic Toxicology and Pharmacology, Chung Yuan Christian University, Chung-Li, Taoyuan City 320314, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wehrle, J., and von Bubnoff, N. 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