AlzPlatform: An Alzheimer's Disease Domain-Specific Chemogenornics Knowledgebase for Polypharmacology and Target Identification Research

作者：Liu, Haibin; Wang, Lirong; Lv, Mingliang; Pei, Rongrong; Li, Peibo; Pei, Zhong; Wang, Yonggang; Su, Weiwei^*; Xie, Xiang Qun

来源：Journal of Chemical Information and Modeling, 2014, 54(4): 1050-1060.

DOI：10.1021/ci500004h

• AlzPlatform
• An Alzheimer’s
• Identification Research

Alzheimer's 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's 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 Target Hunter, 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 405 188 chemicals associated with 1 023 137 records of reported bioactivities from 38 284 corresponding bioassays and 10 050 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 Target Hunter 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.

• 出版日期2014-4
• 单位中山大学