数据加载中.....
|
jsp.display-item.identifier=請使用永久網址來引用或連結此文件:
https://irlib.pccu.edu.tw/handle/987654321/50421
|
| 题名: | Investigating Potential Cardiovascular Toxicity of Two Anti-Leukemia Drugs of Asciminib and Ponatinib in Zebrafish Embryos |
| 作者: | Lin, Huan-Chau
Saputra, Ferry
Audira, Gilbert
Lai, Yu-Heng等 |
| 贡献者: | Department of Chemistry |
| 关键词: | anti-cancer drug
asciminib
cardiovascular toxicity
molecular docking
ponatinib
zebrafish |
| 日期: | 2022-10 |
| 上传时间: | 2022-11-22 15:45:49 (UTC+8) |
| 出版者: | MDPI |
| 摘要: | 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. |
| 關聯: | International Journal of Molecular Sciences 開放取用卷 23, 期 19October 2022 論文號碼 11711 |
| 显示于类别: | [化學系所] 期刊論文
|
文件中的档案:
| 档案 |
描述 |
大小 | 格式 | 浏览次数 |
|---|
| index.html | | 0Kb | HTML | 237 | 检视/开启 |
|
在CCUR中所有的数据项都受到原著作权保护.
|
