Home LiteratureArticle Details
PMID: 21358738 Published · ppublish English Review

Impact of high-throughput screening in biomedical research.

Nature reviews. Drug discovery ·Vol. 10 ·No. 3 ·2011-00-00 ·Pages 188-95

Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, Garyantes T, Green DV, Hertzberg RP, Janzen WP, Paslay JW, Schopfer U, Sittampalam GS

Abstract

High-throughput screening (HTS) has been postulated in several quarters to be a contributory factor to the decline in productivity in the pharmaceutical industry. Moreover, it has been blamed for stifling the creativity that drug discovery demands. In this article, we aim to dispel these myths and present the case for the use of HTS as part of a proven scientific tool kit, the wider use of which is essential for the discovery of new chemotypes.

MeSH Terms
Animals Biomedical Research Drug Design Drug Evaluation, Preclinical/standards,statistics & numerical data Humans Small Molecule Libraries
Chemicals
Small Molecule Libraries
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Macarron Ricardo
Department of Sample Management Technologies, GlaxoSmithKline, Mail Stop UP 12-200, 1250S Collegeville Rd, Collegeville, Pennsylvania 19426, USA. ricardo.macarron@gsk.com
Banks Martyn N
Bojanic Dejan
Burns David J
Cirovic Dragan A
Garyantes Tina
Green Darren V S
Hertzberg Robert P
Janzen William P
Paslay Jeff W
Schopfer Ulrich
Sittampalam G Sitta
References (57)
57 references, click to expand
  1. Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics.
    J Med Chem. 2002 Aug 15;45(17):3573-5 PMID: 12166928
  2. High-content analysis of kinase activity in cells.
    Comb Chem High Throughput Screen. 2008 Aug;11(7):523-36 PMID: 18694389
  3. Current in vitro kinase assay technologies: the quest for a universal format.
    Curr Drug Discov Technol. 2008 Mar;5(1):59-69 PMID: 18537568
  4. Evaluation of division-arrested cells for cell-based high-throughput screening and profiling.
    J Biomol Screen. 2005 Sep;10(6):615-23 PMID: 16103416
  5. Evolution of cell-based reagent provision.
    Drug Discov Today. 2007 Oct;12(19-20):820-5 PMID: 17933682
  6. Cryopreserved cells facilitate cell-based drug discovery.
    Drug Discov Today. 2007 Jul;12(13-14):521-6 PMID: 17631245
  7. Process validation and screen reproducibility in high-throughput screening.
    J Biomol Screen. 2009 Jan;14(1):66-76 PMID: 19171922
  8. Pursuing the leadlikeness concept in pharmaceutical research.
    Curr Opin Chem Biol. 2004 Jun;8(3):255-63 PMID: 15183323
  9. Rebuilding the R&D engine in big pharma.
    Harv Bus Rev. 2008 May;86(5):68-70, 72-6, 128 PMID: 18543809
  10. Enhancements of screening collections to address areas of unmet medical need: an industry perspective.
    Curr Opin Chem Biol. 2010 Jun;14(3):289-98 PMID: 20413343
  11. Hit and lead generation: beyond high-throughput screening.
    Nat Rev Drug Discov. 2003 May;2(5):369-78 PMID: 12750740
  12. Drug repositioning: identifying and developing new uses for existing drugs.
    Nat Rev Drug Discov. 2004 Aug;3(8):673-83 PMID: 15286734
  13. A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays.
    J Biomol Screen. 1999;4(2):67-73 PMID: 10838414
  14. The influence of lead discovery strategies on the properties of drug candidates.
    Nat Rev Drug Discov. 2009 Mar;8(3):203-12 PMID: 19247303
  15. Discovery of JANUVIA (Sitagliptin), a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
    Curr Top Med Chem. 2007;7(6):557-68 PMID: 17352677
  16. Discovery and development of sorafenib: a multikinase inhibitor for treating cancer.
    Nat Rev Drug Discov. 2006 Oct;5(10):835-44 PMID: 17016424
  17. Driving drug discovery: the fundamental role of academic labs.
    Sci Transl Med. 2010 May 5;2(30):30cm16 PMID: 20445199
  18. Virtual exploration of the chemical universe up to 11 atoms of C, N, O, F: assembly of 26.4 million structures (110.9 million stereoisomers) and analysis for new ring systems, stereochemistry, physicochemical properties, compound classes, and drug discovery.
    J Chem Inf Model. 2007 Mar-Apr;47(2):342-53 PMID: 17260980
  19. An analysis of the binding efficiencies of drugs and their leads in successful drug discovery programs.
    J Med Chem. 2010 Apr 8;53(7):2986-97 PMID: 20235539
  20. G-protein coupled receptor assays: to measure affinity or efficacy that is the question.
    Comb Chem High Throughput Screen. 2005 Jun;8(4):285-92 PMID: 16101004
  21. 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor.
    J Med Chem. 2006 Nov 16;49(23):6819-32 PMID: 17154512
  22. The art of the chemical probe.
    Nat Chem Biol. 2010 Mar;6(3):159-161 PMID: 20154659
  23. Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics.
    J Med Chem. 2002 Aug 15;45(17):3576-8 PMID: 12166929
  24. Lessons from 60 years of pharmaceutical innovation.
    Nat Rev Drug Discov. 2009 Dec;8(12):959-68 PMID: 19949401
  25. Can the pharmaceutical industry reduce attrition rates?
    Nat Rev Drug Discov. 2004 Aug;3(8):711-5 PMID: 15286737
  26. The A, B, Cs of G-protein-coupled receptor pharmacology in assay development for HTS.
    Expert Opin Drug Discov. 2007 May;2(5):603-19 PMID: 23488953
  27. Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect.
    Nature. 2010 May 6;465(7294):96-100 PMID: 20410884
  28. An efficient method for the detection and elimination of systematic error in high-throughput screening.
    Bioinformatics. 2007 Jul 1;23(13):1648-57 PMID: 17463024
  29. The completed human genome: implications for chemical biology.
    Curr Opin Chem Biol. 2003 Aug;7(4):511-5 PMID: 12941427
  30. How to improve R&D productivity: the pharmaceutical industry's grand challenge.
    Nat Rev Drug Discov. 2010 Mar;9(3):203-14 PMID: 20168317
  31. Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis.
    J Med Chem. 2001 Oct 25;44(22):3730-45 PMID: 11606138
  32. Overcoming the obstacles in the pharma/biotech industry: 2009 update.
    Drug News Perspect. 2010 Jan-Feb;23(1):48-63 PMID: 20155219
  33. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase.
    Science. 1994 Aug 19;265(5175):1093-5 PMID: 8066447
  34. Application of division arrest technology to cell-based HTS: comparison with frozen and fresh cells.
    Assay Drug Dev Technol. 2005 Feb;3(1):17-26 PMID: 15798392
  35. Functional cell-based assays in microliter volumes for ultra-high throughput screening.
    Comb Chem High Throughput Screen. 2008 Aug;11(7):495-504 PMID: 18694386
  36. Defining and maintaining a high quality screening collection: the GSK experience.
    Drug Discov Today. 2006 Mar;11(5-6):267-72 PMID: 16580604
  37. Key aspects of the Novartis compound collection enhancement project for the compilation of a comprehensive chemogenomics drug discovery screening collection.
    Curr Top Med Chem. 2005;5(4):397-411 PMID: 15892682
  38. From 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk](1,4)benzodiazepin-2(1H)-one (TIBO) to etravirine (TMC125): fifteen years of research on non-nucleoside inhibitors of HIV-1 reverse transcriptase.
    J Med Chem. 2005 Mar 24;48(6):1689-96 PMID: 15771411
  39. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity.
    Antimicrob Agents Chemother. 2005 Nov;49(11):4721-32 PMID: 16251317
  40. Cellular assays as portals to seven-transmembrane receptor-based drug discovery.
    Nat Rev Drug Discov. 2009 Aug;8(8):617-26 PMID: 19609267
  41. Do structurally similar molecules have similar biological activity?
    J Med Chem. 2002 Sep 12;45(19):4350-8 PMID: 12213076
  42. Design of a compound screening collection for use in high throughput screening.
    Comb Chem High Throughput Screen. 2004 Feb;7(1):63-70 PMID: 14965262
  43. Confocal fluorescence microscopy for high-throughput screening of G-protein coupled receptors.
    Curr Med Chem. 2005;12(22):2551-9 PMID: 16248815
  44. Case study: impact of technology investment on lead discovery at Bristol-Myers Squibb, 1998-2006.
    Drug Discov Today. 2008 Jan;13(1-2):44-51 PMID: 18190863
  45. Molecular biology. Industrial-style screening meets academic biology.
    Science. 2008 Aug 8;321(5890):764-6 PMID: 18687934
  46. Fluorescence techniques: shedding light on ligand-receptor interactions.
    Trends Pharmacol Sci. 2000 Jul;21(7):266-73 PMID: 10871895
  47. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist.
    Exp Hematol. 2005 Jan;33(1):85-93 PMID: 15661401
  48. A standard operating procedure for assessing liquid handler performance in high-throughput screening.
    J Biomol Screen. 2002 Dec;7(6):554-69 PMID: 14599354
  49. Identification of hepatitis C virus NS5A inhibitors.
    J Virol. 2010 Jan;84(1):482-91 PMID: 19812153
  50. OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist.
    Science. 1991 Apr 26;252(5005):572-4 PMID: 1850553
  51. Drug discovery in jeopardy.
    J Clin Invest. 2006 Nov;116(11):2837-42 PMID: 17080187
  52. Who wants to be irrational?
    Drug Discov Today. 2003 Aug 1;8(15):655-6 PMID: 12927499
  53. Is there a difference between leads and drugs? A historical perspective.
    J Chem Inf Comput Sci. 2001 Sep-Oct;41(5):1308-15 PMID: 11604031
  54. Structure-based design of HIV protease inhibitors: 4-hydroxycoumarins and 4-hydroxy-2-pyrones as non-peptidic inhibitors.
    J Med Chem. 1994 Sep 30;37(20):3200-4 PMID: 7932546
  55. High-throughput screening: update on practices and success.
    J Biomol Screen. 2006 Oct;11(7):864-9 PMID: 16973922
  56. G-protein-coupled receptors in drug discovery: nanosizing using cell-free technologies and molecular biology approaches.
    J Biomol Screen. 2005 Dec;10(8):765-79 PMID: 16234342
  57. Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists.
    J Med Chem. 1996 May 24;39(11):2123-8 PMID: 8667356
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1784
DOI
10.1038/nrd3368
Email
ricardo.macarron@gsk.com
Published
2011-00-00
Pages
188-95
Language
English
Region
England
NLM ID
101124171
Subset
IM
External Links
PubMed source DOI: 10.1038/nrd3368 View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2