Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors
文献类型：期刊论文
| 作者 | Yan, Chao1,2; Zhang, Qian1,2; Xiao, Pan1,3; Xie, Xinyun1,2; Li, Ming1,2; Qiu, Yuanlai1,2; Wen, Liufa1,2; Song, Xiaomin1,2,4; Dong, Ze1,2; Yang, Cai-Guang1,2,4,5
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| 刊名 | ISRAEL JOURNAL OF CHEMISTRY
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| 出版日期 | 2024-02-15 |
| 页码 | 13 |
| ISSN号 | 0021-2148 |
| 关键词 | RNA modification m(6)A FTO anticancer |
| DOI | 10.1002/ijch.202300166 |
| 通讯作者 | Dong, Ze(dongze@ucas.ac.cn) ; Yang, Cai-Guang(yangcg@simm.ac.cn) |
| 英文摘要 | The biological role of the fat mass and obesity-associated protein (FTO) in the initiation and progress of acute myeloid leukemia (AML) has been elucidated, and several representative FTO inhibitors can markedly suppress the proliferation of AML cells. We previously developed FTO inhibitors including FB23. In this study, we adopted bioisosteric replacement of the intramolecular hydrogen bond in FB23 with a sulfur-oxygen interaction to generate a series of 2-(arylthio)benzoic acid FTO inhibitors and established their structure-activity relationships. Compound 8c was the most potent 2-(arylthio)benzoic acid FTO inhibitor with an IC(50 )value of 0.3 +/- 0.1 mu M, which was comparable with that of FB23 in vitro. To enhance the antiproliferative effects in AML cell lines, we applied a prodrug strategy and prepared some esters. 7l, the methyl ester of 8l, exerted a superior inhibitory effect on a panel of AML cancer cell lines. Additionally, 7l treatment notably increased global m(6)A abundance in AML cells. Collectively, our data suggest that 2-(arylthio)benzoic acid may be a new lead compound for inhibition of FTO, and the prodrug analog exhibit potential in the treatment of AML. |
| WOS关键词 | DEMETHYLASE ; RNA ; M(6)A ; DESIGN |
| 资助项目 | Instrumentation and Service Center for Molecular Sciences at Westlake University ; National Key Research and Development Program of China[2022YFC2705005] ; National Natural Science Foundation of China[22077133] ; National Natural Science Foundation of China[21725801] ; National Natural Science Foundation of China[92153303] ; Youth Innovation Promotion Association of CAS[2021277] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| WOS记录号 | WOS:001162886900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309593]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Dong, Ze; Yang, Cai-Guang |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Hubei Univ, Sch Life Sci, State Key Lab Biocatalysis & Enzyme Engn, Wuhan 430062, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yan, Chao,Zhang, Qian,Xiao, Pan,et al. Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors[J]. ISRAEL JOURNAL OF CHEMISTRY,2024:13. |
| APA | Yan, Chao.,Zhang, Qian.,Xiao, Pan.,Xie, Xinyun.,Li, Ming.,...&Yang, Cai-Guang.(2024).Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors.ISRAEL JOURNAL OF CHEMISTRY,13. |
| MLA | Yan, Chao,et al."Structure-Activity Relationships of 2-(Arylthio)benzoic Acid FTO Inhibitors".ISRAEL JOURNAL OF CHEMISTRY (2024):13. |
入库方式： OAI收割
来源：上海药物研究所
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