Label-free screening assays: A strategy for finding better drug candidates

Future Medicinal Chemistry

Volumn 2, Issue 11, 2010, Pages 1703-1716

  Lunn, Charles A ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RECOMBINANT DNA;

AUTOMATION; CELL LABELING; DRUG DETERMINATION; DRUG INDUSTRY; DRUG TARGETING; ELECTROMAGNETIC FIELD; GEL PERMEATION CHROMATOGRAPHY; HIGH THROUGHPUT SCREENING; LABEL FREE ASSAY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLOMICS; OPTICAL BIOSENSOR; PRIORITY JOURNAL; PROTEIN PURIFICATION; PROTEOMICS; REVIEW;

ANIMALS; AUTOMATION; BIOSENSING TECHNIQUES; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MASS SPECTROMETRY; MOLECULAR STRUCTURE; PHARMACEUTICAL PREPARATIONS;

EID: 78649288013     PISSN: 17568919     EISSN: None     Source Type: Journal    
DOI: 10.4155/fmc.10.246     Document Type: Review

References (114)

1. Kenakin T, Miller LJ. Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery. Pharmacol. Rev. 62(2), 265-304 (2010).
2. Smith RG, Sestili MA. Methods for ligand-receptor assays in clinical chemistry. Clin. Chem. 26(5), 543-550 (1980).
3. Hart HE, Greenwald EB. Scintillation proximity assay (SPA)- a new method of immunoassay. Direct and inhibition mode detection with human albumin and rabbit antihuman albumin. Mol. Immunol. 16(4), 265-267 (1979).
4. Udenfriend S, Gerber LD, Brink L, Spector S. Scintillation proximity radioimmunoassay utilizing 125I-labeled ligands. Proc. Natl Acad. Sci. USA 82(24), 8672-8676 (1985).
5. Hoffman R, Cameron L. Characterization of a scintillation proximity assay to detect modulators of transforming growth factor a (TGFa) binding. Anal. Biochem. 203, 70-75 (1992).
6. Jessop RA. Imaging proximity assays. Proc. SPIE 3259, 228-233 (1998).
7. TM technology to measure [35s]gtpys binding to chinese hamster ovary cell membranes expressing the cloned human 5-HTIB receptor. J. Biomol. Screen. 3, 101-105 (1998).
8. Carpenter JW, Laethem C, Hubbard FR et al. Confguring radioligand receptor binding assays for HTS using scintillation proximity assay technology. Methods Mol. Biol. 190, 31-49 (2002).
9. Glickman JF, Schmid A, Ferrand S. Scintillation proximity assays in high-throughput screening. Assay Drug Dev. Technol. 6(3), 433-455 (2008).
10. Schroeder KS, Neagle BD. FLIPR: a new instrument for accurate, high throughput optical screening. J. Biomolec. Screen. 1(2), 75-80 (1996).
11. Glaser V. An interview with Kirk S. Schroeder, President, Essen Instruments. Assay Drug Develop. Technol. 1, 3-8 (2002).
12. Ullman EF, Kirakossian H, Singh S et al. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc. Natl Acad. Sci. USA 91(12), 5426-5430 (1994).
13. Glickman JF, Wu X, Mercuri R et al. A comparison of ALPHAScreen, TR-FRET, and TRF as assay methods for FXR nuclear receptors. J. Biomol. Screen. 7(1), 3-10 (2002).
14. Golla R, Seethala R. A homogeneous enzyme fragment complementation cyclic AMP screen for GPCR agonists. J. Biomol. Screen. 7(6), 515-525 (2002).
15. Michael S, Auld D, Klumpp C et al. A robotic platform for quantitative high-throughput screening. Assay Drug. Dev. Technol. 6(5), 637-657 (2008).
16. Hook DJ. Team building and leadership in the successful implementation of automation for high-throughput screening. J. Auto. Chem. 18(4), 131-134 (1996).
17. Munos B. Lessons from 60 years of pharmaceutical innovation. Nat. Rev. Drug Discov. 8(12), 959-968 (2009).
18. Kola I. The state of innovation in drug development. Clin. Pharmacol. Ther. 83(2), 227-230 (2008).
19. Paolini GV, Shapland RH, van Hoorn W P, Mason JS, Hopkins AL. Global mapping of pharmacological space. Nat. Biotechnol. 24(7), 805-815 (2006).
20. Hollinger MA. Introduction to Pharmacology (2nd Edition) Taylor and Francis, NY, USA, 6 (2003).
21. Kirschner MH. All Medicines are Poison! Author House, IN, USA, 4 (2009).
22. European research group of Morgan Stanley. Laboratory Equipment Magazine 12 March (2010).
23. Huggett B. Still strapped for cash. Nat. Biotech. 27(6), 493 (2009).
24. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954), 191-196 (2003).
25. Milne JC, Lambert PD, Schenk S et al. Small molecule activators of SIRT1 as therapeutics for treatment of Type 2 diabetes. Nature 450, 712-716 (2007).
26. Borra MT, Smith BC, Denu JM. Mechanism of human SIRT1 activation by resveratrol. J. Biol. Chem. 280(17), 17187-17195 (2005).
27. Kaeberlein M, McDonagh T, Heltweg B et al. Substrate-specifc activation of sirtuins by resveratrol. J. Biol. Chem. 280(17), 17038-17045 (2005).
28. Pacholec M, Bleasdale JE, Chrunyk B et al. SRT1720, SRT2183, SRT1460, and Resveratrol are not direct activators of SIRT1. J. Biol. Chem. 285, 8340-8351 (2010).
29. Beher D, Wu J, Cumine S et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem. Biol. Drug Des. 74(6), 619-624 (2009).
30. Yan SF, King FJ, He Y, Caldwell JS, Zhou Y. Learning from the data: mining of large high-throughput screening databases. J. Chem. Inf. Model 46(6), 2381-2395 (2006).
31. Xie XQ, Chen JZ. Data mining a small-molecule drug screening representative subset from NIH PubChem. J. Chem. Inf. Model 48(3), 465-475 (2008).
32. Kostenis E, Waelbroeck M, Milligan G. Techniques: promiscuous Ga proteins in basic research and drug discovery. Trends Pharmacol. Sci. 26(11), 595-602 (2005).
33. Zehender H, Le Goff F, Lehmann N, Filipuzzi I, Mayr LM. SpeedScreen: the 'missing link' between genomics and lead discovery. J. Biomol. Screen. 9, 498-505 (2004).
34. Brown N, Zehender H, Azzaoui K, Schuffenhauer A, Mayr LM, Jacoby E. A chemoinformatics ana lysis of hit lists obtained from high-throughput affnity-selection screening. J. Biomol. Screen. 11(2), 123-130 (2006).
35. Annis DA, Nazef N, Chuang CC, Scott MP, Nash HM. A general technique to rank protein-ligand binding affnities and determine allosteric versus direct binding site competition in compound mixtures. J. Am. Chem. Soc. 126(47), 15495-15503 (2004).
36. Coburn CA, Stachel SJ, Li YM et al. Identifcation of a small molecule nonpeptide active site b-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases. J. Med. Chem. 47(25), 6117-6119 (2004).
37. Annis DA, Nazef N, Chuang CC, Scott MP, Nash HM. A general technique to rank protein-ligand binding affnities and determine allosteric versus direct binding site competition in compound mixtures. J. Am. Chem. Soc. 126(47), 15495-15503 (2004).
38. Whitehurst CE, Nazef N, Annis DA et al. Discovery and characterization of orthosteric and allosteric muscarinic M2 acetylcholine receptor ligands by affnity selection-mass spectrometry. J. Biomol. Screen. 11(2), 194-207 (2006).
39. Annis DA, Shipps GW Jr, Deng Y et al. Method for quantitative protein-ligand affnity measurements in compound mixtures. Anal. Chem. 79(12), 4538-4542 (2007).
40. Zheng H, Loh HH, Law PY. Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications. IUBMB Life 62(2), 112-119 (2010).
41. Groebe DR. Screening for positive allosteric modulators of biological targets. Drug Discov. Today 11(13-14), 632-639 (2006).
42. Groebe DR. In search of negative allosteric modulators of biological targets. Drug Discov. Today 14(1-2), 41-49 (2009).
43. Roddy TP, Horvath CR, Stout SJ et al. Mass spectrometric techniques for label-free high-throughput screening in drug discovery. Anal. Chem. 79(21), 8207-8213 (2007).
44. Zhang JH, Roddy TP, Ho PI et al. Assay development and screening of human DGAT1 inhibitors with an LC/MS-based assay: application of mass spectrometry for large-scale primary screening. J. Biomol. Screen. 15(6), 695-702 (2010) (Epub).
45. Quercia AK, LaMarr WA, Myung J, Ozbal CC, Landro JA, Lumb KJ. High-throughput screening by mass spectrometry: comparison with the scintillation proximity assay with a focused-fle screen of AKT1/ PKB a. J. Biomol. Screen. 12(4), 473-480 (2007).
46. Ozbal CC, LaMarr WA, Linton JR et al. High-throughput screening via mass spectrometry: a case study using acetylcholinesterase. Assay Drug Dev. Technol. 2(4), 373-381 (2004).
47. Forbes CD, Toth JG, Ozbal CC et al. High-throughput mass spectrometry screening for inhibitors of phosphatidylserine decarboxylase. J. Biomol. Screen. 12(5), 628-634 (2007).
48. Soulard P, McLaughlin M, Stevens J et al. Development of a high-throughput screening assay for stearoyl-coa desaturase using rat liver microsomes, deuterium labeled stearoyl-coa and mass spectrometry. Analytica Chimica Acta. 627(1), 105-111 (2008).
49. Jonas M, LaMarr WA, Ozbal C. Mass spectrometry in high-throughput screening: a case study on acetyl-coenzyme a carboxylase using RapidFire - mass spectrometry (RF-MS). Comb. Chem. High Throughput Screen. 12(8), 752-759 (2009).
50. Lim KB, Ozbal CC, Kassel DB. Development of a high-throughput online solid-phase extraction/tandem mass spectrometry method for cytochrome P450 inhibition screening. J. Biomol. Screen. 15(4), 447-452 (2010).
51. Motlekar N, Diamond SL, Napper AD. Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteases. Assay Drug Dev. Technol. 6(3), 395-405 (2008).
52. Langsdorf EF, Malikzay A, Lamarr WA et al. Screening for antibacterial inhibitors of the UDP-3 -O- (R-3 -hydroxy my ristoyl)-N-acetylglucosamine deacetylase (LpxC) using a high-throughput mass spectrometry assay. J. Biomol. Screen. 15(1), 52-61 (2010).
53. Cummings MD, Farnum MA, Nelen MI. Universal screening methods and applications of ThermoFluor. J. Biomol. Screen. 11(7), 854-863 (2006).
54. Clare J J. Targeting ion channels for drug discovery. Discov. Med. 9(46), 253-260 (2010).
55. Milligan G, Kostenis E. Heterotrimeric G-proteins: a short history. Br. J. Pharmacol. 147(Suppl. 1), S46-S55 (2006).
56. Mailman RB. GPCR functional selectivity has therapeutic impact. Trends Pharmacol. Sci. 28(8), 390-396 (2007).
57. Zheng H, Loh HH, Law PY. Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications. IUBMB Life 62(2), 112-119 (2010).
58. Prather PL, Martin NA, Breivogel CS, Childers SR. Activation of cannabinoid receptors in rat brain by WIN 55212-2 produces coupling to multiple G protein a-subunits with different potencies. Mo l. Pharmacol. 57(5), 1000-1010 (2000).
59. Houston DB, Howlett AC. Differential receptor-G-protein coupling evoked by dissimilar cannabinoid receptor agonists. Cell Signal. 10(9), 667-674 (1998).
60. Rajagopal S, Rajagopal K, Lefkowitz RJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat. Rev. Drug Discov. 9(5), 373-386 (2010).
61. Ferré S, Goldberg SR, Lluis C, Franco R. Looking for the role of cannabinoid receptor heteromers in striatal function. Neuropharmacology 56 (Suppl 1), 226-234 (2009).
62. Sexton PM, Poyner DR, Simms J, Christopoulos A, Hay DL. Modulating receptor function through RAMPs: can they represent drug targets in themselves? Drug Discov. Today. 14(7-8), 413-419 (2009).
63. Traynor J. Regulator of G protein-signaling proteins and addictive drugs. Ann. NY Acad. Sci. 1187, 341-352 (2010).
64. Maudsley S, Martin B, Luttrell LM. G protein-coupled receptor signaling complexity in neuronal tissue: implications for novel therapeutics. Curr. Alzheimer Res. 4(1), 3-19 (2007).
65. Galandrin S, Oligny-Longpré G, Bouvier M. The evasive nature of drug effcacy: implications for drug discovery. Trends Pharmacol. Sci. 28(8), 423-430 (2007).
66. Banerjee P, Franz B, Bhunia AK. Mammalian cell-based sensor system. Adv. Biochem. Eng Biotechnol. 117, 2155 (2010).
67. Cabral GA, Griffn-Thomas L. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinfammation. Expert Rev. Mol. Med. 11, e3 (2009).
68. Idris AI, van 't Hof RJ, Greig IR et al Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat. Med. 11(7), 774-779 (2005).
69. Idris AI, Sophocleous A, Landao-Bassonga E, van't Hof RJ, Ralston SH. Regulation of bone mass, osteoclast function and ovariectomy-induced bone loss by the type 2 cannabinoid receptor. Endocrinology. 149(11), 5619-5626 (2008).
70. Ofek O, Karsak M, Leclerc N et al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc. Natl Acad. Sci. USA 103(3), 696-701 (2006).
71. Lunn CA, Fine J, Rojas-Triana A et al. Cannabinoid CB(2)-selective inverse agonist protects against antigen-induced bone loss. Immunopharmacol. Immunotoxicol. 29(3-4), 387-401 (2007).
72. Lozano-Ondoua AN, Wright C, Vardanyan A et al. A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sci. 86(17-18), 646-653 (2010).
73. Geng D, Xu Y, Yang H et al. Protection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonist. Biomaterials 31(8), 1996-2000 (2010).
74. Ni X, Geller EB, Eppihimer MJ, Eisenstein TK, Adler MW, Tuma RF. Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model. Mult. Scler. 10(2), 158-164 (2004).
75. Maresz K, Pryce G, Ponomarev ED et al. Direct suppression of CNS autoimmune infammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat. Med. 13(4), 492-497 (2007).
76. Sipe JC, Arbour N, Gerber A, Beutler E. Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2) receptor gene polymorphism: possible risk for autoimmune disorders. J. Leukoc. Biol. 78(1), 231-238 (2005).
77. Palazuelos J, Davoust N, Julien B et al. The CB (2) cannabinoid receptor controls myeloid progenitor traffcking: involvement in the pathogenesis of an animal model of multiple sclerosis. J. Biol. Chem. 283(19), 13320-13329 (2008).
78. Lunn CA, Reich EP, Fine JS et al. Biology and therapeutic potential of cannabinoid CB2 receptor inverse agonists. Br. J. Pharmacol. 153(2), 226-239 (2008).
79. Lunn CA. Updating the chemistry and biology of cannabinoid CB(2) receptor-specifc inverse agonists. Curr. Top. Med. Chem. 10(8), 768-778 (2010).
80. Cotton M, Claing A. G protein-coupled receptors stimulation and the control of cell migration. Cell Signal. 21(7), 1045-1053 (2009).
81. DeFea K. p-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction. Br. J. Pharmacol. 153(Suppl. 1), S298-S309 (2008).
82. Ganguly S, Pucadyil TJ, Chattopadhyay A. Actin cytoskeleton-dependent dynamics of the human serotonin 1A receptor correlates with receptor signaling. Biophys. J. 95(1), 451-463 (2008).
83. Johnson EN. High throughput screening follow-up studies using physiologically relevant cells. Am. Drug Discov. 3(2), 12-22 (2007).
84. Cunningham BT, Li P, Schulz S et al. Label-free assays on the BIND system. J. Biomol. Screen. 9(6), 481-490 (2004).
85. Fang Y, Ferrie AM, Li G. Probing cytoskeleton modulation by optical biosensors. FEBS Lett. 579(19), 4175-4180 (2005).
86. Verdonk E, Johnson K, McGuinness R et al. Cellular dielectric spectroscopy: a label-free comprehensive platform for functional evaluation of endogenous receptors. Assay Drug Dev. Technol. 4(5), 609-619 (2006).
87. Solly K, Wang X, Xu X, Strulovici B, Zheng W. Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays. Assay Drug Dev. Technol. 2(4), 363-372 (2004).
88. Lee PH, Gao A, Van Staden C et al. Evaluation of dynamic mass redistribution technology for pharmacological studies of recombinant and endogenously expressed G protein-coupled receptors. Assay Drug Dev. Technol. 6, 83-94 (2008).
89. Yu N, Atienza JM, Bernard J et al. Real-time monitoring of morphological changes in living cells by electronic cell sensor arrays: an approach to study G protein-coupled receptors. Anal. Chem. 78, 35-43 (2006).
90. Peters MF, Knappenberger KS, Wilkins D et al. Evaluation of cellular dielectric spectroscopy, a whole-cell, label-free technology for drug discovery on Gi-coupled GPCRs. J. Biomol. Screen. 12, 312-319 (2007).
91. Peters MF, Scott CW Evaluating cellular impedance assays for detection of GPCR pleiotropic signaling and functional selectivity J. Biomol. Screen. 14, 246-255 (2009).
92. Peters MF, Vaillancourt F, Heroux M, Valiquette M, Scott CW. Comparing label-free biosensors for pharmacological screening with cell-based functional assays. Assay Drug Dev. Technol. 8(2), 219-227 (2010).
93. Du Y, Li Z, Li L et al. Distinct growth factor-induced dynamic mass redistribution (DMR) profles for monitoring oncogenic signaling pathways in various cancer cells. J. Recept. Signal. Trans. 29(3-4), 182-194 (2009).
94. Fang Y, Ferrie AM. Label-free optical biosensor for ligand-directed functional selectivity acting on p(2) adrenoceptor in living cells. FEBS Lett. 582(5), 558-564 (2008).
95. Dodgson K, Gedge L, Murray DC, Coldwell M. A 100K well screen for a muscarinic receptor using the Epic® label-free system - a refection on the benefts of the label-free approach to screening seven-transmembrane receptors. J. Recept. Signal Trans. 29(3-4), 163-172 (2009).
96. Begley S, Carmichael M. Desperately seeking cures. Newsweek. May 24 & 31, 38-42 (2010).
97. Rathore R, Pribil P, Corr JJ, Seibel WL, Evdokimov A, Greis KD. Multiplex enzyme assays and inhibitor screening by mass spectrometry. J. Biomol. Screen. 15(8), 1001-1007 (2010) (Epub).
98. Bowen BP, Northen TR. Dealing with the unknown: metabolomics and metabolite atlases. J. Am. Soc. Mass. Spectrom. 21(9), 1471-1476 (2010).
99. Young NL, Plazas-Mayorca MD, Garcia BA. Systems-wide proteomic characterization of combinatorial post-translational modifcation patterns. Expert Rev. Proteomics. 7(1), 79-92 (2010).
100. Wang D, Bodovitz S. Single cell ana lysis: the new frontier in 'omics'. Trends Biotechnol. 28(6), 281-290 (2010). (Epub).
101. Baxter MA, Rowe C, Alder J et al. Generating hepatic cell lineages from pluripotent stem cells for drug toxicity screening. Stem Cell Res. 5(1), 4-22 (2010).
102. Murata M, Tohyama S, Fukuda K. Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery. Pharmacol. Ther. 126(2), 109-118 (2010).
103. Phillips BW, Crook JM. Pluripotent human stem cells: a novel tool in drug discovery. BioDrugs 24(2), 99-108 (2010).
104. Sano Y, Shimizu F, Abe M et al. Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function. J. Cell. Physiol. 225(2), 519-528 (2010).
105. Gu Y, Li H, Miki J et al. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines. Exp. Cell Res. 312(6), 831-843 (2006).
106. Brandt S. TERT over-expression affects the growth of myocardial tissue derived from mouse embryonic stem cells. Differentiation, 79(1), 1-8 (2010).
107. Cheung PY, Deng W, Man C et al. Genetic alterations in a telomerase-immortalized human esophageal epithelial cell line: implications for carcinogenesis. Cancer Lett. 293(1), 41-51 (2010).
108. ® Scanner: low cell number applications in cytotoxicity, chemotaxis and differentiation. Presented at: SBS 16th Annual Conference & Exhibition, Phoenix, AZ, USA, 13 April 2010.
109. Huang WE, Li M, Jarvis RM, Goodacre R, Banwart SA. Shining light on the microbial world the application of Raman microspectroscopy. Adv. Appl. Microbiol. 70, 153-186 (2010).
110. Wachsmann-Hogiu S, Weeks T, Huser T. Chemical ana lysis in vivo and in vitro by Raman spectroscopy - from single cells to humans. Curr. Opin. Biotechnol. 20(1), 63-73 (2009).
111. Bleicher KH, Böhm HJ, Müller K, Alanine AI. Hit and lead generation: beyond high-throughput screening. Nat. Rev. Drug Discov. 2(5), 369-378 (2003).
112. Keseru GM, Makara GM. Hit discovery and hit-to-lead approaches. Drug Discov. Today 11(15-16), 741-748 (2006).
113. Feng BY, Shoichet BK. Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures. J. Med. Chem. 49(7), 2151-2154 (2006).
114. Jadhav A, Ferreira RS, Klumpp C et al. Quantitative analyses of aggregation, autofuorescence and reactivity artifacts in a screen for inhibitors of a thiol protease. J. Med. Chem. 53(1), 37-51 (2010).