Open access high throughput drug discovery in the public domain: a Mount Everest in the making.

High throughput screening (HTS) facilitates screening large numbers of compounds against a biochemical target of interest using validated biological or biophysical assays. In recent years, a significant number of drugs in clinical trails originated from HTS campaigns, validating HTS as a bona fide mechanism for hit finding. In the current drug discovery landscape, the pharmaceutical industry is embracing open innovation strategies with academia to maximize their research capabilities and to feed their drug discovery pipeline. The goals of academic research have therefore expanded from target identification and validation to probe discovery, chemical genomics, and compound library screening. This trend is reflected in the emergence of HTS centers in the public domain over the past decade, ranging in size from modestly equipped academic screening centers to well endowed Molecular Libraries Probe Centers Network (MLPCN) centers funded by the NIH Roadmap initiative. These centers facilitate a comprehensive approach to probe discovery in academia and utilize both classical and cutting-edge assay technologies for executing primary and secondary screening campaigns. The various facets of academic HTS centers as well as their implications on technology transfer and drug discovery are discussed, and a roadmap for successful drug discovery in the public domain is presented. New lead discovery against therapeutic targets, especially those involving the rare and neglected diseases, is indeed a Mount Everestonian size task, and requires diligent implementation of pharmaceutical industry's best practices for a successful outcome.

[1]  E. Krausz,et al.  Cell-based high-content screening of small-molecule libraries. , 2007, Current opinion in chemical biology.

[2]  Xiao Xu,et al.  The application of cell‐based label‐free technology in drug discovery , 2008, Biotechnology journal.

[3]  John P. Overington,et al.  How many drug targets are there? , 2006, Nature Reviews Drug Discovery.

[4]  T. Insel,et al.  NIH Molecular Libraries Initiative , 2004, Science.

[5]  Tudor I. Oprea,et al.  A crowdsourcing evaluation of the NIH chemical probes. , 2009, Nature chemical biology.

[6]  Sitta Sittampalam,et al.  High throughput screening in academia - Drug discovery initiatives at the University of Kansas , 2008 .

[7]  R. Mariuzza,et al.  Luxury accommodations: the expanding role of structural plasticity in protein-protein interactions. , 2000, Structure.

[8]  Sophie Dahan,et al.  Current Screens Based on the AlphaScreen™ Technology for Deciphering Cell Signalling Pathways , 2009, Current genomics.

[9]  J. Frearson,et al.  HTS and hit finding in academia – from chemical genomics to drug discovery , 2009, Drug discovery today.

[10]  Christopher P Austin,et al.  High-throughput screening assays for the identification of chemical probes. , 2007, Nature chemical biology.

[11]  Youwen Zhou,et al.  The US Orphan Drug Act: rare disease research stimulator or commercial opportunity? , 2010, Health policy.

[12]  A. Hopkins,et al.  The druggable genome , 2002, Nature Reviews Drug Discovery.

[13]  Mark B. Carter,et al.  Flow cytometry for drug discovery, receptor pharmacology and high-throughput screening. , 2007, Current opinion in pharmacology.

[14]  Christopher P Austin,et al.  The impact of the completed human genome sequence on the development of novel therapeutics for human disease. , 2004, Annual review of medicine.

[15]  Zhiyuan Hu,et al.  SPR imaging for high throughput, label-free interaction analysis. , 2009, Combinatorial chemistry & high throughput screening.

[16]  Eva J Gordon Small-molecule screening: it takes a village... , 2007, ACS chemical biology.

[17]  M. Sakharkar,et al.  Targetability of human disease genes. , 2007, Current drug discovery technologies.

[18]  P. Kassner,et al.  RNAi for the discovery of novel oncology targets : a critical evaluation , 2009 .

[19]  B. Munos Lessons from 60 years of pharmaceutical innovation , 2009, Nature Reviews Drug Discovery.

[20]  Philip Denner,et al.  High-content analysis in preclinical drug discovery. , 2008, Combinatorial chemistry & high throughput screening.

[21]  Nathanael S Gray,et al.  Drug discovery through industry-academic partnerships , 2006, Nature chemical biology.

[22]  Jonathan Knowles,et al.  A guide to drug discovery: Target selection in drug discovery , 2003, Nature Reviews Drug Discovery.

[23]  Simon Frantz How academia can help drug discovery , 2004, Nature Reviews Drug Discovery.

[24]  Michelle R. Arkin,et al.  Small-molecule inhibitors of protein–protein interactions: progressing towards the dream , 2004, Nature Reviews Drug Discovery.