Cheminformatics and Drug Repurposing

The symposium took place on Sunday, August 19, 2012 from 1:30 PM until approximately 5:30 PM in the Philadelphia Marriott Downtown hotel. Seven speakers from industry, academia and other research labs shared their leading expertise in the area with over 50 attendees. The speakers presented opinions, case studies, and perspectives of this increasingly attractive topic to the Chemical Information community and other research areas.

Chris Lipinski (Consultant for Melior Discovery, USA) opened the symposium providing a broad perspective of the current status of the success of drug discovery efforts. Chris raised the question: “What is wrong with drug discovery?” He then reflected that one of the failures of drug discovery efforts is the current single-target approach. In this context, drug repurposing or drug repositioning is based on an alternative multi-targeted approach. Chris pointed out that a vast number of resources that are available in the public domain are promising for drug repurposing efforts in industry and other research organizations.

Thomas Freeman (Boehringer-Ingelheim, USA) spoke about the current areas of improvement of drug discovery from an industry point of view. He emphasized that the biology involved in the drug development efforts is highly complex and then discussed three major approaches to mine the vast amount of accumulated data for drug repurposing: biological, chemical, and textual data mining. Freeman presented case studies that exemplify the success of these approaches.

Iwona Weidlich (University of Maryland, USA) discussed a comprehensive study conducted in an academic setting to identify approved drugs with HCV RNA polymerase activity. She described a general computational approach to develop predictive QSAR models for molecules in a training set and then apply such models to mine databases of approved drugs. Iwona also covered key aspects of the database preparation, generation of predictive models, and shared personal experiences that face academia conducting drug repurposing projects.

Joshua Swamidass (Washington University in St. Louis, USA), also from an academic point of view, talked about opportunities and challenges that drug repurposing faces. He presented a rigorous statistical-based approach to predict potential biological activities starting from sparse and incomplete data matrices of chemical databases annotated with biological activity across different targets.

Antony Williams of the Royal Society of Chemistry and one of the lead developers of ChemSpider, discussed in detail the Open PHACTS project, a large initiative to mine publicly available databases such as PubChem, ChemSpider, BindingDB, for drug repurposing using cheminformatics tools. He also discussed issues of standards and data validation in available databases which is one significant issue with which OpenPHACTS will deal. The slides from his presentation are available at his slideshare.

Dongsup Kim (Department of Bio and Brain Engineering, KAIST, Republic of Korea), presented the development and applications of the drug-drug relationship score (DRS) for use to predict drug pairs that share common targets. This drug relationship score can then successfully be applied as a predictive method for new target identification and has successfully predicted pharmacological effects.

Mohamed Abdul Hameed (Biotechnology High Performance Computing Software Applications Institute, USA) closed the symposium presenting the results of a general target fishing strategy based on 3D similarity searching. He described both the validation of the approach using a well-known data set of decoy compounds and then the application of the validated approach for drug repurposing.

Two papers could not be presented due to unavoidable travel conflicts for the presenters, Richard Cramer (Tripos, USA) and Chenglong Li (The Ohio State University, USA).

José Medina-Franco and Rachelle Bienstock, Symposium Organizers