Global mapping of pharmacological space.
We present the global mapping of pharmacological space by the integration of several vast sources of medicinal chemistry structure-activity relationships (SAR) data. Our comprehensive mapping of pharmacological space enables us to identify confidently the human targets for which chemical tools and drugs have been discovered to date. The integration of SAR data from diverse sources by unique canonical chemical structure, protein sequence and disease indication enables the construction of a ligand-target matrix to explore the global relationships between chemical structure and biological targets. Using the data matrix, we are able to catalog the links between proteins in chemical space as a polypharmacology interaction network. We demonstrate that probabilistic models can be used to predict pharmacology from a large knowledge base. The relationships between proteins, chemical structures and drug-like properties provide a framework for developing a probabilistic approach to drug discovery that can be exploited to increase research productivity.
Paolini
Gaia V
GV
The Department of Knowledge Discovery, Pfizer Global Research and Development, Sandwich, Kent CT13 9NJ, UK.
Shapland
Richard H B
RH
van Hoorn
Willem P
WP
Mason
Jonathan S
JS
Hopkins
Andrew L
AL
D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D016208:Databases, Factual; D030562:Databases, Protein; D006801:Humans; D008956:Models, Chemical; D008961:Models, Structural; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010602:Pharmacopoeias as Topic / Q000145:classification; D013329:Structure-Activity Relationship
D004364:Pharmaceutical Preparations