Discover Novel Covalent Inhibitors Targeting FLT3 through Hybrid Virtual Screening Strategy
文献类型：期刊论文
| 作者 | Hu, Shengquan1; Liu, Jing1; Chen, Sikang1; Gao, Jian1; Zhou, Yubo2 ; Liu, Tao1; Dong, Xiaowu1,3,4
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| 刊名 | BIOLOGICAL & PHARMACEUTICAL BULLETIN
 |
| 出版日期 | 2021-12-01 |
| 卷号 | 44期号:12页码:1872-1877 |
| 关键词 | acute myeloid leukemia FMS-like tyrosine kinase 3 CovDock hybrid virtual screening autodock |
| ISSN号 | 0918-6158 |
| DOI | 10.1248/bpb.b21-00579 |
| 通讯作者 | Dong, Xiaowu(dongxw@aju.edu.cn) |
| 英文摘要 | FMS-like tyrosine kinase 3 (FLT3) plays a very important role in regulating the proliferation, differentiation and survival of normal hematopoietic stem cells. Internal tandem duplications of the FLT3 gene (FLT3-ITD) mutations are present in 25% of all acute myeloid leukemia (AML) patients and are frequently associated with adverse clinical outcomes. Therefore, FLT3-ITD is a promising target for the treatment of AML. The use of covalent virtual screenings has shown that efficient rational approaches for the rapid discovery of new drugs scaffold. Herein, we report a hybrid virtual screening strategy that led to the discovery of FLT3 inhibitors. Using the combination of non-covalent docking and covalent docking, 8 compounds were found to inhibit FLT3, and G856-8335, S346-0154 are also effective against mutant FLT3. These two compounds also show selectivity to receptor tyrosine kinase (C-KIT), which has the potential for optimization. And this work can be extended to the screening of other covalent inhibitors. |
| WOS关键词 | ACTIVATION ; RESISTANCE ; MECHANISM ; FUTURE ; D835 |
| 资助项目 | China Postdoctoral Science Foundation[2020M671768] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000755081400011 |
| 出版者 | PHARMACEUTICAL SOC JAPAN |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300427]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Dong, Xiaowu |
| 作者单位 | 1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou Inst Innovat Med, Inst Drug Discovery & Design, Hangzhou 310058, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Zhejiang Univ, Canc Ctr, Hangzhou 310058, Peoples R China 4.Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Hangzhou 310016, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Shengquan,Liu, Jing,Chen, Sikang,et al. Discover Novel Covalent Inhibitors Targeting FLT3 through Hybrid Virtual Screening Strategy[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2021,44(12):1872-1877. |
| APA | Hu, Shengquan.,Liu, Jing.,Chen, Sikang.,Gao, Jian.,Zhou, Yubo.,...&Dong, Xiaowu.(2021).Discover Novel Covalent Inhibitors Targeting FLT3 through Hybrid Virtual Screening Strategy.BIOLOGICAL & PHARMACEUTICAL BULLETIN,44(12),1872-1877. |
| MLA | Hu, Shengquan,et al."Discover Novel Covalent Inhibitors Targeting FLT3 through Hybrid Virtual Screening Strategy".BIOLOGICAL & PHARMACEUTICAL BULLETIN 44.12(2021):1872-1877. |
入库方式： OAI收割
来源：上海药物研究所
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