In silico off-target profiling for enhanced drug safety assessment
文献类型：期刊论文
| 作者 | Liu, Jin4,5; Gui, Yike2,4; Rao, Jingxin3,4; Sun, Jingjing3,4; Wang, Gang3,4; Ren, Qun2,4; Qu, Ning3,4; Niu, Buying3,4; Chen, Zhiyi3,4; Sheng, Xia3,4 |
| 刊名 | ACTA PHARMACEUTICA SINICA B
 |
| 出版日期 | 2024-07-01 |
| 卷号 | 14期号:7页码:2927-2941 |
| 关键词 | Drug safety Off-target prediction Adverse drug reactions Toxicity Molecular representation Artificial intelligence |
| ISSN号 | 2211-3835 |
| DOI | 10.1016/j.apsb.2024.03.002 |
| 通讯作者 | Zheng, Mingyue(myzheng@simm.ac.cn) ; Li, Xutong(lixutong@simm.ac.cn) |
| 英文摘要 | Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases. However, the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial. Drug off-target interactions, along with the adverse drug reactions they induce, are significant factors affecting drug safety. To assess the liability of candidate drugs, we developed an artificial intelligence model for the precise prediction of compound off-target interactions, leveraging multi-task graph neural networks. The outcomes of off-target predictions can serve as representations for compounds, enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity. Furthermore, the predicted off-target profiles are employed in adverse drug reaction (ADR) enrichment analysis, facilitating the inference of potential ADRs for a drug. Using the withdrawn drug Pergolide as an example, we elucidate the mechanisms underlying ADRs at the target level, contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions. Overall, our work facilitates the early assessment of compound safety/toxicity based on off-target identification, deduces potential ADRs of drugs, and ultimately promotes the secure development of drugs. |
| WOS关键词 | LARGE-SCALE PREDICTION ; PHARMACOLOGY ; PHENYLPROPANOLAMINE ; ASSOCIATION ; RECEPTORS ; PIPELINE ; PROTEIN ; ASTHMA |
| 资助项目 | National Natural Science Foundation of China[T2225002] ; National Natural Science Foundation of China[82273855] ; National Natural Science Foundation of China[82204278] ; National Natural Science Foundation of China[LG202102-01-02] ; National Natural Science Foundation of China[E2G805H] ; Shanghai Municipal Science and Technology Major Project |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001265412400001 |
| 出版者 | INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/312285]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Zheng, Mingyue; Li, Xutong |
| 作者单位 | 1.Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 330106, Peoples R China 2.Nanjing Univ Chinese Med, Nanjing 210023, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Jin,Gui, Yike,Rao, Jingxin,et al. In silico off-target profiling for enhanced drug safety assessment[J]. ACTA PHARMACEUTICA SINICA B,2024,14(7):2927-2941. |
| APA | Liu, Jin.,Gui, Yike.,Rao, Jingxin.,Sun, Jingjing.,Wang, Gang.,...&Li, Xutong.(2024).In silico off-target profiling for enhanced drug safety assessment.ACTA PHARMACEUTICA SINICA B,14(7),2927-2941. |
| MLA | Liu, Jin,et al."In silico off-target profiling for enhanced drug safety assessment".ACTA PHARMACEUTICA SINICA B 14.7(2024):2927-2941. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。