| Autor: |
Shan-Liang Sun, Jia-Zhen Wu, Jing-Jing Wang, Hai Zhou, Chen-Qian Zhang, Zhen-Jiang Tong, Yi-Bo Wang, Jiu-Kai Sha, Qing-Xin Wang, Jia-Chuan Liu, Xin-Rui Zheng, Qing-Qing Li, Meng-Yuan Zhang, Jin Yang, Tian-Hua Wei, Zi-Xuan Wang, Yan-Cheng Yu, Ning Ding, Xue-Jiao Leng, Xin Xue, He-Min Li, Wei-Chen Dai, Xiao-Ying Yin, Ye Yang, Jin-Ao Duan, Nian-Guang Li, Zhi-Hao Shi |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Biomedicine & Pharmacotherapy, Vol 169, Iss , Pp 115905- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
0753-3322 |
| DOI: |
10.1016/j.biopha.2023.115905 |
| Popis: |
The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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