Literature DB >> 21644825

Growing PAINS in academic drug discovery.

Adrian Whitty1.   

Abstract

In a recent article it was argued that compounds published as drug leads by academic laboratories commonly contain functionality that identifies them as nonspecific 'pan-assay interference compounds' (PAINS). The article raises broad questions about why best practices for hit and lead qualification that are well known in industry are not more widely employed in academia, as well as about the role of journals in publishing manuscripts that report drug leads of little potential value. Barriers to adoption of best practices for some academic drug-discovery researchers include knowledge gaps and infrastructure deficiencies, but they also arise from fundamental differences in how academic research is structured and how success is measured. Academic drug discovery should not seek to become identical to commercial pharmaceutical research, but we can do a better job of assessing and communicating the true potential of the drug leads we publish, thereby reducing the wastage of resources on nonviable compounds.

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Year:  2011        PMID: 21644825      PMCID: PMC3667403          DOI: 10.4155/fmc.11.44

Source DB:  PubMed          Journal:  Future Med Chem        ISSN: 1756-8919            Impact factor:   3.808


  15 in total

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Authors:  Olivier Roche; Petra Schneider; Jochen Zuegge; Wolfgang Guba; Manfred Kansy; Alexander Alanine; Konrad Bleicher; Franck Danel; Eva-Maria Gutknecht; Mark Rogers-Evans; Werner Neidhart; Henri Stalder; Michael Dillon; Eric Sjögren; Nader Fotouhi; Paul Gillespie; Robert Goodnow; William Harris; Phil Jones; Mikio Taniguchi; Shinji Tsujii; Wolfgang von der Saal; Gerd Zimmermann; Gisbert Schneider
Journal:  J Med Chem       Date:  2002-01-03       Impact factor: 7.446

2.  A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening.

Authors:  Susan L McGovern; Emilia Caselli; Nikolaus Grigorieff; Brian K Shoichet
Journal:  J Med Chem       Date:  2002-04-11       Impact factor: 7.446

3.  Assessment of the consistency of medicinal chemists in reviewing sets of compounds.

Authors:  Michael S Lajiness; Gerald M Maggiora; Veerabahu Shanmugasundaram
Journal:  J Med Chem       Date:  2004-09-23       Impact factor: 7.446

4.  ALARM NMR: a rapid and robust experimental method to detect reactive false positives in biochemical screens.

Authors:  Jeffrey R Huth; Renaldo Mendoza; Edward T Olejniczak; Robert W Johnson; Darlene A Cothron; Yaya Liu; Claude G Lerner; Jun Chen; Philip J Hajduk
Journal:  J Am Chem Soc       Date:  2005-01-12       Impact factor: 15.419

5.  A detergent-based assay for the detection of promiscuous inhibitors.

Authors:  Brian Y Feng; Brian K Shoichet
Journal:  Nat Protoc       Date:  2006       Impact factor: 13.491

6.  In silico ADMET traffic lights as a tool for the prioritization of HTS hits.

Authors:  Mario Lobell; Martin Hendrix; Berthold Hinzen; Jörg Keldenich; Heinrich Meier; Carsten Schmeck; Rudolf Schohe-Loop; Tobias Wunberg; Alexander Hillisch
Journal:  ChemMedChem       Date:  2006-11       Impact factor: 3.466

Review 7.  Between a rock and a hard place?

Authors:  Adrian Whitty; Gnanasambandam Kumaravel
Journal:  Nat Chem Biol       Date:  2006-03       Impact factor: 15.040

Review 8.  Targeting protein-protein interactions: lessons from p53/MDM2.

Authors:  Justin K Murray; Samuel H Gellman
Journal:  Biopolymers       Date:  2007       Impact factor: 2.505

Review 9.  The resurgence of covalent drugs.

Authors:  Juswinder Singh; Russell C Petter; Thomas A Baillie; Adrian Whitty
Journal:  Nat Rev Drug Discov       Date:  2011-04       Impact factor: 84.694

10.  Promiscuous aggregate-based inhibitors promote enzyme unfolding.

Authors:  Kristin E D Coan; David A Maltby; Alma L Burlingame; Brian K Shoichet
Journal:  J Med Chem       Date:  2009-04-09       Impact factor: 7.446

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  21 in total

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Journal:  Expert Opin Investig Drugs       Date:  2016-02-16       Impact factor: 6.206

Review 2.  Protein lysine acetylation by p300/CBP.

Authors:  Beverley M Dancy; Philip A Cole
Journal:  Chem Rev       Date:  2015-01-16       Impact factor: 60.622

3.  Enhancing Molecular Promiscuity Evaluation Through Assay Profiles.

Authors:  Sorin Avram; Ramona Curpan; Alina Bora; Cristian Neanu; Liliana Halip
Journal:  Pharm Res       Date:  2018-10-18       Impact factor: 4.200

Review 4.  Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases.

Authors:  Vladimir N Uversky; Vrushank Davé; Lilia M Iakoucheva; Prerna Malaney; Steven J Metallo; Ravi Ramesh Pathak; Andreas C Joerger
Journal:  Chem Rev       Date:  2014-05-15       Impact factor: 60.622

Review 5.  Therapeutic strategies to inhibit MYC.

Authors:  Michael R McKeown; James E Bradner
Journal:  Cold Spring Harb Perspect Med       Date:  2014-10-01       Impact factor: 6.915

6.  Drug discovery in an academic setting: playing to the strengths.

Authors:  Donna M Huryn
Journal:  ACS Med Chem Lett       Date:  2013-01-17       Impact factor: 4.345

7.  Structure-Guided Synthesis and Mechanistic Studies Reveal Sweetspots on Naphthyl Salicyl Hydrazone Scaffold as Non-Nucleosidic Competitive, Reversible Inhibitors of Human Ribonucleotide Reductase.

Authors:  Sarah E Huff; Faiz Ahmad Mohammed; Mu Yang; Prashansa Agrawal; John Pink; Michael E Harris; Chris G Dealwis; Rajesh Viswanathan
Journal:  J Med Chem       Date:  2018-01-05       Impact factor: 7.446

8.  A sensitive luminescent assay for the histone methyltransferase NSD1 and other SAM-dependent enzymes.

Authors:  Katherine M Drake; Venita G Watson; Anne Kisielewski; Rebecca Glynn; Andrew D Napper
Journal:  Assay Drug Dev Technol       Date:  2014-06       Impact factor: 1.738

Review 9.  Therapeutic Potential of Spirooxindoles as Antiviral Agents.

Authors:  Na Ye; Haiying Chen; Eric A Wold; Pei-Yong Shi; Jia Zhou
Journal:  ACS Infect Dis       Date:  2016-05-05       Impact factor: 5.084

Review 10.  Contributions of academic laboratories to the discovery and development of chemical biology tools.

Authors:  Donna M Huryn; Lynn O Resnick; Peter Wipf
Journal:  J Med Chem       Date:  2013-05-31       Impact factor: 7.446

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