AlzPlatform: An Alzheimer鈥檚 Disease Domain-Specific Chemogenomics Knowledgebase for Polypharmacology and Target Identification Research

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• 作者：Haibin Liu ; Lirong Wang ; Mingliang Lv ; Rongrong Pei ; Peibo Li ; Zhong Pei ; Yonggang Wang ; Weiwei Su ; Xiang-Qun Xie
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2014
• 出版时间：April 28, 2014
• 年：2014
• 卷：54
• 期：4
• 页码：1050-1060
• 全文大小：808K
• 年卷期：v.54,no.4(April 28, 2014)
• ISSN：1549-960X

文摘

Alzheimer鈥檚 disease (AD) is one of the most complicated progressive neurodegeneration diseases that involve many genes, proteins, and their complex interactions. No effective medicines or treatments are available yet to stop or reverse the progression of the disease due to its polygenic nature. To facilitate discovery of new AD drugs and better understand the AD neurosignaling pathways involved, we have constructed an Alzheimer鈥檚 disease domain-specific chemogenomics knowledgebase, AlzPlatform (www.cbligand.org/AD/) with cloud computing and sourcing functions. AlzPlatform is implemented with powerful computational algorithms, including our established TargetHunter, HTDocking, and BBB Predictor for target identification and polypharmacology analysis for AD research. The platform has assembled various AD-related chemogenomics data records, including 928 genes and 320 proteins related to AD, 194 AD drugs approved or in clinical trials, and 405鈥?88 chemicals associated with 1鈥?23鈥?37 records of reported bioactivities from 38鈥?84 corresponding bioassays and 10鈥?50 references. Furthermore, we have demonstrated the application of the AlzPlatform in three case studies for identification of multitargets and polypharmacology analysis of FDA-approved drugs and also for screening and prediction of new AD active small chemical molecules and potential novel AD drug targets by our established TargetHunter and/or HTDocking programs. The predictions were confirmed by reported bioactivity data and our in vitro experimental validation. Overall, AlzPlatform will enrich our knowledge for AD target identification, drug discovery, and polypharmacology analyses and, also, facilitate the chemogenomics data sharing and information exchange/communications in aid of new anti-AD drug discovery and development.