Open Access High Throughput Drug Discovery in the Public Domain: A Mount Everest in the Making

Anuradha      Roy; Peter      R. McDonald; Sitta      Sittampalam; Rathnam      Chaguturu

Abstract

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 industrys best practices for a successful outcome.

Keywords: High throughput screening, open innovation, drug discovery, academia, NIH Roadmap, EU-OpenScreen, target identification, probe discovery, intellectual property, new chemical entities, screening and data production, data analysis and dissemination, technology develop-ment, Molecular Libraries Pro-gram (MLP), Molecular Libraries Screening Centers Net-work (MLSCN), Molecular Libraries Probe Production Centers Network (MLPCN), ultra high throughput screening, high content screening, high-throughput microscopy, high con-tent analysis, Surface plasmon resonance, Enzyme-linked immunosorbent assays, fluorescence polarization, AlphaScreen, AlphaLI-SA, lactate dehydrogenase, heterogeneous cell viability assessment, heterogeneous absorbance-based LDH as-say, homogenous absorbance-based LDH assay, luminescence cyto-toxicity assay, Pipeline Pilot scientific data workflow platform, Activity base XE enable custom data processing, COX-2 inhibitor