Literature DB >> 20809896

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

Anuradha Roy1, 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 industry's best practices for a successful outcome.

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Year:  2010        PMID: 20809896      PMCID: PMC3716285          DOI: 10.2174/138920110792927757

Source DB:  PubMed          Journal:  Curr Pharm Biotechnol        ISSN: 1389-2010            Impact factor:   2.837


  25 in total

Review 1.  Target discovery.

Authors:  Mark A Lindsay
Journal:  Nat Rev Drug Discov       Date:  2003-10       Impact factor: 84.694

2.  How academia can help drug discovery.

Authors:  Simon Frantz
Journal:  Nat Rev Drug Discov       Date:  2004-07       Impact factor: 84.694

Review 3.  Small-molecule inhibitors of protein-protein interactions: progressing towards the dream.

Authors:  Michelle R Arkin; James A Wells
Journal:  Nat Rev Drug Discov       Date:  2004-04       Impact factor: 84.694

Review 4.  How many drug targets are there?

Authors:  John P Overington; Bissan Al-Lazikani; Andrew L Hopkins
Journal:  Nat Rev Drug Discov       Date:  2006-12       Impact factor: 84.694

5.  Drug discovery through industry-academic partnerships.

Authors:  Nathanael S Gray
Journal:  Nat Chem Biol       Date:  2006-12       Impact factor: 15.040

Review 6.  Cell-based high-content screening of small-molecule libraries.

Authors:  Kerstin Korn; Eberhard Krausz
Journal:  Curr Opin Chem Biol       Date:  2007-10-10       Impact factor: 8.822

7.  The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?

Authors:  Olivier Wellman-Labadie; Youwen Zhou
Journal:  Health Policy       Date:  2009-12-29       Impact factor: 2.980

Review 8.  Lessons from 60 years of pharmaceutical innovation.

Authors:  Bernard Munos
Journal:  Nat Rev Drug Discov       Date:  2009-12       Impact factor: 84.694

9.  A crowdsourcing evaluation of the NIH chemical probes.

Authors:  Tudor I Oprea; Cristian G Bologa; Scott Boyer; Ramona F Curpan; Robert C Glen; Andrew L Hopkins; Christopher A Lipinski; Garland R Marshall; Yvonne C Martin; Liliana Ostopovici-Halip; Gilbert Rishton; Oleg Ursu; Roy J Vaz; Chris Waller; Herbert Waldmann; Larry A Sklar
Journal:  Nat Chem Biol       Date:  2009-07       Impact factor: 15.040

10.  Current Screens Based on the AlphaScreen Technology for Deciphering Cell Signalling Pathways.

Authors:  Saïd Taouji; Sophie Dahan; Roger Bossé; Eric Chevet
Journal:  Curr Genomics       Date:  2009-04       Impact factor: 2.236

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  24 in total

1.  Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1.

Authors:  Ying Wang; David M Lonard; Yang Yu; Dar-Chone Chow; Timothy G Palzkill; Jin Wang; Ruogu Qi; Alexander J Matzuk; Xianzhou Song; Franck Madoux; Peter Hodder; Peter Chase; Patrick R Griffin; Suoling Zhou; Lan Liao; Jianming Xu; Bert W O'Malley
Journal:  Cancer Res       Date:  2014-01-03       Impact factor: 12.701

2.  Prediction of drug combination effects with a minimal set of experiments.

Authors:  Aleksandr Ianevski; Anil K Giri; Prson Gautam; Alexander Kononov; Swapnil Potdar; Jani Saarela; Krister Wennerberg; Tero Aittokallio
Journal:  Nat Mach Intell       Date:  2019-12-09

Review 3.  Shifting from the single to the multitarget paradigm in drug discovery.

Authors:  José L Medina-Franco; Marc A Giulianotti; Gregory S Welmaker; Richard A Houghten
Journal:  Drug Discov Today       Date:  2013-01-20       Impact factor: 7.851

4.  MScreen: an integrated compound management and high-throughput screening data storage and analysis system.

Authors:  Renju T Jacob; Martha J Larsen; Scott D Larsen; Paul D Kirchhoff; David H Sherman; Richard R Neubig
Journal:  J Biomol Screen       Date:  2012-06-15

5.  Data Mining and Computational Modeling of High-Throughput Screening Datasets.

Authors:  Sean Ekins; Alex M Clark; Krishna Dole; Kellan Gregory; Andrew M Mcnutt; Anna Coulon Spektor; Charlie Weatherall; Nadia K Litterman; Barry A Bunin
Journal:  Methods Mol Biol       Date:  2018

6.  High-throughput screening for small-molecule modulators of inward rectifier potassium channels.

Authors:  Rene Raphemot; C David Weaver; Jerod S Denton
Journal:  J Vis Exp       Date:  2013-01-27       Impact factor: 1.355

Review 7.  Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities.

Authors:  Jurjan Aman; Ester M Weijers; Geerten P van Nieuw Amerongen; Asrar B Malik; Victor W M van Hinsbergh
Journal:  Am J Physiol Lung Cell Mol Physiol       Date:  2016-06-24       Impact factor: 5.464

8.  Metadata Standard and Data Exchange Specifications to Describe, Model, and Integrate Complex and Diverse High-Throughput Screening Data from the Library of Integrated Network-based Cellular Signatures (LINCS).

Authors:  Uma D Vempati; Caty Chung; Chris Mader; Amar Koleti; Nakul Datar; Dušica Vidović; David Wrobel; Sean Erickson; Jeremy L Muhlich; Gabriel Berriz; Cyril H Benes; Aravind Subramanian; Ajay Pillai; Caroline E Shamu; Stephan C Schürer
Journal:  J Biomol Screen       Date:  2014-02-11

9.  Computational prediction and validation of an expert's evaluation of chemical probes.

Authors:  Nadia K Litterman; Christopher A Lipinski; Barry A Bunin; Sean Ekins
Journal:  J Chem Inf Model       Date:  2014-10-07       Impact factor: 4.956

10.  Screening of Conditionally Reprogrammed Patient-Derived Carcinoma Cells Identifies ERCC3-MYC Interactions as a Target in Pancreatic Cancer.

Authors:  Natalya Beglyarova; Eugenia Banina; Yan Zhou; Ramilia Mukhamadeeva; Grigorii Andrianov; Egor Bobrov; Elena Lysenko; Natalya Skobeleva; Linara Gabitova; Diana Restifo; Max Pressman; Ilya G Serebriiskii; John P Hoffman; Keren Paz; Diana Behrens; Vladimir Khazak; Sandra A Jablonski; Erica A Golemis; Louis M Weiner; Igor Astsaturov
Journal:  Clin Cancer Res       Date:  2016-07-06       Impact factor: 12.531

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