Application of deep generative model for design of Pyrrolo[2,3-d] pyrimidine derivatives as new selective TANK binding kinase 1 (TBK1) inhibitors
文献类型：期刊论文
| 作者 | Song, Shukai5; Tang, Haotian1,4; Ran, Ting3; Fang, Feng4; Tong, Linjiang4; Chen, Hongming3; Xie, Hua2,4 ; Lu, Xiaoyun5
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2023-02-05 |
| 卷号 | 247页码:115034 |
| 关键词 | SyntaLinker Generative modelling TBK1 inhibitor pyrrolo[2 3-d]pyrimidine Structure-activity relationship |
| DOI | 10.1016/j.ejmech.2022.115034 |
| 文献子类 | Article |
| 英文摘要 | The deep conditional transformer neural network SyntaLinker was applied to identify compounds with pyrrolo [2,3-d]pyrimidine scaffold as potent selective TBK1 inhibitor. Further medicinal chemistry optimization campaign led to the discovery of the most potent compound 7l, which exhibited strong enzymatic inhibitory activity against TBK1 with an IC50 value of 22.4 nM 7l had a superior inhibitory activity in human monocytic THP1-Blue cells reporter gene assay than MRT67307. Furthermore, 7l significantly inhibited TBK1 downstream target genes cxcl10 and ifn beta expression in THP1 and RAW264.7 cells induced by poly (I:C) and lipopolysac-charide, respectively. This study suggested that combination of deep conditional transformer neural network SyntaLinker and transfer learning could be a powerful tool for scaffold hopping in drug discovery. |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| WOS记录号 | WOS:000961129400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309723]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Hongming; Xie, Hua; Lu, Xiaoyun |
| 作者单位 | 1.Univ Chinese Acad Sci, 19 A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan, Peoples R China; 3.Div Drug & Vaccine Res, Guangzhou Lab, Guangzhou 510530, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 5.Jinan Univ, Sch Pharm, 855 Xingye Ave, Guangzhou 510632, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Song, Shukai,Tang, Haotian,Ran, Ting,et al. Application of deep generative model for design of Pyrrolo[2,3-d] pyrimidine derivatives as new selective TANK binding kinase 1 (TBK1) inhibitors[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2023,247:115034. |
| APA | Song, Shukai.,Tang, Haotian.,Ran, Ting.,Fang, Feng.,Tong, Linjiang.,...&Lu, Xiaoyun.(2023).Application of deep generative model for design of Pyrrolo[2,3-d] pyrimidine derivatives as new selective TANK binding kinase 1 (TBK1) inhibitors.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,247,115034. |
| MLA | Song, Shukai,et al."Application of deep generative model for design of Pyrrolo[2,3-d] pyrimidine derivatives as new selective TANK binding kinase 1 (TBK1) inhibitors".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 247(2023):115034. |
入库方式： OAI收割
来源：上海药物研究所
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