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抗癫痫药物重新定位的系统方法。

Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs.

作者信息

Ko Younhee, Lee Chulho, Lee Youngmok, Lee Jin-Sung

机构信息

Division of Biomedical Engineering, Hankuk University of Foreign Studies, Kyoungki-do 17035, Korea.

Department of Clinical Genetics, Department of Pediatrics, Yonsei University, College of Medicine, Seoul 03722, Korea.

出版信息

Diagnostics (Basel). 2019 Nov 30;9(4):208. doi: 10.3390/diagnostics9040208.

Abstract

Epilepsy is a central neurological disorder affecting individuals of all ages and causing unpredictable seizures. In spite of the improved efficacy of new antiepileptic drugs and novel therapy, there are still approximately 20%~30% of patients, who have either intractable or uncontrolled seizures. The epilepsy drug-target network (EDT) is constructed and successfully demonstrates the characteristics and efficacy of popularly used AEDs through the identification of causative genes for 60 epilepsy patients. We discovered that the causative genes of most intractable patients were not the targets of existing AEDs, as well as being very far from the etiological mechanisms of existing AEDs in the functional networks. We show that the existence of new drugs that target the causative genes of intractable epilepsy patients, which will be potential candidates for refractory epilepsy patients. Our systematic approach demonstrates a new possibility for drug repositioning through the combination of the drug-target and functional networks.

摘要

癫痫是一种中枢神经系统疾病,影响各个年龄段的人群,并导致不可预测的癫痫发作。尽管新型抗癫痫药物和新疗法的疗效有所提高,但仍有大约20%至30%的患者癫痫发作难以控制或无法得到有效控制。构建了癫痫药物-靶点网络(EDT),并通过鉴定60例癫痫患者的致病基因,成功展示了常用抗癫痫药物的特性和疗效。我们发现,大多数难治性患者的致病基因并非现有抗癫痫药物的靶点,并且在功能网络中与现有抗癫痫药物的病因机制相距甚远。我们表明,针对难治性癫痫患者致病基因的新药的存在,将为难治性癫痫患者提供潜在的候选药物。我们的系统方法通过药物-靶点和功能网络的结合,展示了药物重新定位的新可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afe5/6963462/9a0aa63c872f/diagnostics-09-00208-g001.jpg

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