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Review

Label-Free Screening Assays: A Strategy for Finding Better Drug Candidates

Pages 1703-1716 | Published online: 11 Nov 2010

Bibliography

  • Kenakin T , MillerLJ. 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).
  • Smith RG , SestiliMA. Methods for ligand-receptor assays in clinical chemistry.Clin. Chem.26(5), 543–550 (1980).
  • Hart HE , GreenwaldEB. 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).
  • Udenfriend S , GerberLD, BrinkL, SpectorS. Scintillation proximity radioimmunoassay utilizing 125I-labeled ligands.Proc. Natl Acad. Sci. USA82(24), 8672–8676 (1985).
  • Hoffman R , CameronL. Characterization of a scintillation proximity assay to detect modulators of transforming growth factor α (TGFα) binding.Anal. Biochem.203, 70–75 (1992).
  • Jessop RA . Imaging proximity assays.Proc.SPIE3259, 228–233 (1998).
  • Watson J , SelkirkJV, BrownAM. Development of FlashplateTM 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).
  • Carpenter JW , LaethemC, HubbardFRet al. Configuring radioligand receptor binding assays for HTS using scintillation proximity assay technology. Methods Mol. Biol. 190, 31–49 (2002).
  • Glickman JF , SchmidA, FerrandS. Scintillation proximity assays in high-throughput screening.Assay Drug Dev.Technol.6(3), 433–455 (2008).
  • Schroeder KS , NeagleBD. FLIPR: a new instrument for accurate, high throughput optical screening.J. Biomolec. Screen.1(2), 75–80 (1996).
  • Glaser V . An interview with Kirk S. Schroeder, President, Essen Instruments.Assay Drug Develop. Technol.1, 3–8 (2002).
  • Ullman EF , KirakossianH, SinghSet al. Luminescent oxygen channeling immunoassay: measurement of particle binding kinetics by chemiluminescence. Proc. Natl Acad. Sci. USA 91(12), 5426–5430 (1994).
  • Glickman JF , WuX, MercuriRet al. A comparison of ALPHAScreen, TR-FRET, and TRF as assay methods for FXR nuclear receptors. J. Biomol. Screen. 7(1), 3–10 (2002).
  • Golla R , SeethalaR. A homogeneous enzyme fragment complementation cyclic AMP screen for GPCR agonists.J. Biomol. Screen.7(6), 515–525 (2002).
  • Michael S , AuldD, KlumppCet al. A robotic platform for quantitative high-throughput screening. Assay Drug. Dev. Technol. 6(5), 637–657 (2008).
  • Hook DJ . Team building and leadership in the successful implementation of automation for high-throughput screening.J. Auto. Chem.18(4), 131–134 (1996).
  • Munos B . Lessons from 60 years of pharmaceutical innovation.Nat. Rev. Drug Discov.8(12), 959–968 (2009).
  • Kola I . The state of innovation in drug development.Clin. Pharmacol. Ther.83(2), 227–230 (2008).
  • Paolini GV , ShaplandRH, van Hoorn WP, Mason JS, Hopkins AL. Global mapping of pharmacological space. Nat. Biotechnol.24(7), 805–815 (2006).
  • Hollinger MA . Introduction to Pharmacology (2nd Edition)Taylor and Francis, NY, USA, 6 (2003).
  • Kirschner MH . All Medicines are Poison! Author House, IN, USA, 4 (2009).
  • European research group of Morgan Stanley . Laboratory Equipment Magazine12March (2010).
  • Huggett B . Still strapped for cash.Nat. Biotech.27(6), 493 (2009).
  • Howitz KT , BittermanKJ, CohenHY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature425(6954), 191–196 (2003).
  • Milne JC , LambertPD, SchenkSet al. Small molecule activators of SIRT1 as therapeutics for treatment of Type 2 diabetes. Nature 450, 712–716 (2007).
  • Borra MT , SmithBC, DenuJM. Mechanism of human SIRT1 activation by resveratrol.J. Biol. Chem.280(17), 17187–17195 (2005).
  • Kaeberlein M , McDonaghT, HeltwegBet al. Substrate-specific activation of sirtuins by resveratrol. J. Biol. Chem. 280(17), 17038–17045 (2005).
  • Pacholec M , BleasdaleJE, ChrunykBet al. SRT1720, SRT2183, SRT1460, and Resveratrol are not direct activators of SIRT1. J. Biol. Chem. 285, 8340–8351 (2010).
  • Beher D , WuJ, CumineSet al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem. Biol. Drug Des. 74(6), 619–624 (2009).
  • Yan SF , KingFJ, HeY, CaldwellJS, ZhouY. Learning from the data: mining of large high-throughput screening databases.J. Chem. Inf. Model46(6), 2381–2395 (2006).
  • Xie XQ , ChenJZ. Data mining a small-molecule drug screening representative subset from NIH PubChem.J. Chem. Inf. Model48(3), 465–475 (2008).
  • Kostenis E , WaelbroeckM, MilliganG. Techniques: promiscuous Ga proteins in basic research and drug discovery.Trends Pharmacol. Sci.26(11), 595–602 (2005).
  • 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).
  • Brown N , ZehenderH, AzzaouiK, SchuffenhauerA, MayrLM, JacobyE. A chemoinformatics analysis of hit lists obtained from high-throughput affinity-selection screening.J. Biomol. Screen.11(2), 123–130 (2006).
  • Annis DA , NazefN, ChuangCC, ScottMP, NashHM. A general technique to rank protein–ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures.J. Am. Chem. Soc.126(47), 15495–15503 (2004).
  • Coburn CA , StachelSJ, LiYMet al. Identification of a small molecule nonpeptide active site β-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases. J. Med. Chem. 47(25), 6117–6119 (2004).
  • Annis DA , NazefN, ChuangCC, ScottMP, NashHM. A general technique to rank protein-ligand binding affinities and determine allosteric versus direct binding site competition in compound mixtures.J. Am. Chem. Soc.126(47), 15495–15503 (2004).
  • Whitehurst CE , NazefN, AnnisDAet al. Discovery and characterization of orthosteric and allosteric muscarinic M2 acetylcholine receptor ligands by affinity selection-mass spectrometry. J. Biomol. Screen. 11(2), 194–207 (2006).
  • Annis DA , ShippsGW Jr, Deng Y et al. Method for quantitative protein-ligand affinity measurements in compound mixtures. Anal. Chem.79(12), 4538–4542 (2007).
  • Zheng H , LohHH, LawPY. Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications.IUBMB Life62(2), 112–119 (2010).
  • Groebe DR . Screening for positive allosteric modulators of biological targets.Drug Discov. Today11(13–14), 632–639 (2006).
  • Groebe DR . In search of negative allosteric modulators of biological targets.Drug Discov. Today14(1–2), 41–49 (2009).
  • Roddy TP , HorvathCR, StoutSJet al. Mass spectrometric techniques for label-free high-throughput screening in drug discovery. Anal. Chem. 79(21), 8207–8213 (2007).
  • Zhang JH , RoddyTP, HoPIet 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).
  • Quercia AK , LaMarrWA, MyungJ, OzbalCC, LandroJA, LumbKJ. High-throughput screening by mass spectrometry: comparison with the scintillation proximity assay with a focused-file screen of AKT1/PKB a.J. Biomol. Screen.12(4), 473–480 (2007).
  • Ozbal CC , LaMarrWA, LintonJRet al. High-throughput screening via mass spectrometry: a case study using acetylcholinesterase. Assay Drug Dev. Technol. 2(4), 373–381 (2004).
  • Forbes CD , TothJG, OzbalCCet al. High-throughput mass spectrometry screening for inhibitors of phosphatidylserine decarboxylase. J. Biomol. Screen. 12(5), 628–634 (2007).
  • Soulard P , McLaughlinM, StevensJet 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).
  • Jonas M , LaMarrWA, OzbalC. 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).
  • Lim KB , OzbalCC, KasselDB. 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).
  • Motlekar N , DiamondSL, NapperAD. Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteases.Assay Drug Dev. Technol.6(3), 395–405 (2008).
  • Langsdorf EF , MalikzayA, LamarrWAet al. Screening for antibacterial inhibitors of the UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) using a high-throughput mass spectrometry assay. J. Biomol. Screen. 15(1), 52–61 (2010).
  • Cummings MD , FarnumMA, NelenMI. Universal screening methods and applications of ThermoFluor.J. Biomol. Screen.11(7), 854–863 (2006).
  • Clare JJ . Targeting ion channels for drug discovery.Discov. Med.9(46), 253–260 (2010).
  • Milligan G , KostenisE. Heterotrimeric G-proteins: a short history.Br. J. Pharmacol.147(Suppl. 1), S46–S55 (2006).
  • Mailman RB . GPCR functional selectivity has therapeutic impact.Trends Pharmacol. Sci.28(8), 390–396 (2007).
  • Zheng H , LohHH, LawPY. Agonist-selective signaling of G protein-coupled receptor: mechanisms and implications.IUBMB Life62(2), 112–119 (2010).
  • Prather PL , MartinNA, BreivogelCS, ChildersSR. Activation of cannabinoid receptors in rat brain by WIN 55212–2 produces coupling to multiple G protein α-subunits with different potencies.Mol. Pharmacol.57(5), 1000–1010 (2000).
  • Houston DB , HowlettAC. Differential receptor-G-protein coupling evoked by dissimilar cannabinoid receptor agonists.Cell Signal.10(9), 667–674 (1998).
  • Rajagopal S , RajagopalK, LefkowitzRJ. Teaching old receptors new tricks: biasing seven-transmembrane receptors.Nat. Rev. Drug Discov.9(5), 373–386 (2010).
  • Ferré S , GoldbergSR, LluisC, FrancoR. Looking for the role of cannabinoid receptor heteromers in striatal function.Neuropharmacology56(Suppl 1), 226–234 (2009).
  • Sexton PM , PoynerDR, SimmsJ, ChristopoulosA, HayDL. Modulating receptor function through RAMPs: can they represent drug targets in themselves?Drug Discov. Today.14(7–8), 413–419 (2009).
  • Traynor J . Regulator of G protein-signaling proteins and addictive drugs.Ann. NY Acad. Sci.1187, 341–352 (2010).
  • Maudsley S , MartinB, LuttrellLM. G protein-coupled receptor signaling complexity in neuronal tissue: implications for novel therapeutics.Curr. Alzheimer Res.4(1), 3–19 (2007).
  • Galandrin S , Oligny-LongpréG, BouvierM. The evasive nature of drug efficacy: implications for drug discovery.Trends Pharmacol. Sci.28(8), 423–430 (2007).
  • Banerjee P , FranzB, BhuniaAK. Mammalian cell-based sensor system.Adv. Biochem. Eng. Biotechnol.117, 21–55 (2010).
  • Cabral GA , Griffin-ThomasL. Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation.Expert Rev. Mol. Med.11, e3 (2009).
  • Idris AI , van ‘t HofRJ, GreigIRet al. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat. Med.11(7), 774–779 (2005).
  • Idris AI , SophocleousA, Landao-BassongaE, 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).
  • Ofek O , KarsakM, LeclercNet al. Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc. Natl Acad. Sci. USA 103(3), 696–701 (2006).
  • Lunn CA , FineJ, Rojas-TrianaAet al. Cannabinoid CB(2)-selective inverse agonist protects against antigen-induced bone loss. Immunopharmacol. Immunotoxicol. 29(3–4), 387–401 (2007).
  • Lozano-Ondoua AN , WrightC, VardanyanAet al. A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sci. 86(17–18), 646–653 (2010).
  • Geng D , XuY, YangHet al. Protection against titanium particle induced osteolysis by cannabinoid receptor 2 selective antagonist. Biomaterials 31(8), 1996–2000 (2010).
  • Ni X , GellerEB, EppihimerMJ, EisensteinTK, AdlerMW, TumaRF. Win 55212–2, a cannabinoid receptor agonist, attenuates leukocyte/endothelial interactions in an experimental autoimmune encephalomyelitis model.Mult. Scler.10(2), 158–164 (2004).
  • Maresz K , PryceG, PonomarevEDet al. Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat. Med. 13(4), 492–497 (2007).
  • Sipe JC , ArbourN, GerberA, BeutlerE. 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).
  • Palazuelos J , DavoustN, JulienBet al. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J. Biol. Chem. 283(19), 13320–13329 (2008).
  • Lunn CA , ReichEP, FineJSet al. Biology and therapeutic potential of cannabinoid CB2 receptor inverse agonists. Br. J. Pharmacol. 153(2), 226–239 (2008).
  • Lunn CA . Updating the chemistry and biology of cannabinoid CB(2) receptor-specific inverse agonists.Curr. Top. Med. Chem.10(8), 768–778 (2010).
  • Cotton M , ClaingA. G protein-coupled receptors stimulation and the control of cell migration.Cell Signal.21(7), 1045–1053 (2009).
  • DeFea K . β-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction.Br. J. Pharmacol.153(Suppl. 1), S298–S309 (2008).
  • Ganguly S , PucadyilTJ, ChattopadhyayA. Actin cytoskeleton-dependent dynamics of the human serotonin1A receptor correlates with receptor signaling.Biophys. J.95(1), 451–463 (2008).
  • Johnson EN . High throughput screening follow-up studies using physiologically relevant cells.Am. Drug Discov.3(2), 12–22 (2007).
  • Cunningham BT , LiP, SchulzSet al. Label-free assays on the BIND system. J. Biomol. Screen. 9(6), 481–490 (2004).
  • Fang Y , FerrieAM, LiG. Probing cytoskeleton modulation by optical biosensors.FEBS Lett.579(19), 4175–4180 (2005).
  • Verdonk E , JohnsonK, McGuinnessRet al. Cellular dielectric spectroscopy: a label-free comprehensive platform for functional evaluation of endogenous receptors. Assay Drug Dev. Technol. 4(5), 609–619 (2006).
  • Solly K , WangX, XuX, StruloviciB, ZhengW. Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays.Assay Drug Dev. Technol.2(4), 363–372 (2004).
  • Lee PH , GaoA, 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).
  • Yu N , AtienzaJM, BernardJet 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).
  • Peters MF , KnappenbergerKS, WilkinsDet 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).
  • Peters MF , ScottCW. Evaluating cellular impedance assays for detection of GPCR pleiotropic signaling and functional selectivity.J. Biomol. Screen.14, 246–255 (2009).
  • Peters MF , VaillancourtF, HerouxM, ValiquetteM, ScottCW. Comparing label-free biosensors for pharmacological screening with cell-based functional assays.Assay Drug Dev. Technol.8(2), 219–227 (2010).
  • Du Y , LiZ, LiLet al. Distinct growth factor-induced dynamic mass redistribution (DMR) profiles for monitoring oncogenic signaling pathways in various cancer cells. J. Recept. Signal. Trans. 29(3–4), 182–194 (2009).
  • Fang Y , FerrieAM. Label-free optical biosensor for ligand-directed functional selectivity acting on β(2) adrenoceptor in living cells.FEBS Lett.582(5), 558–564 (2008).
  • Dodgson K , GedgeL, MurrayDC, ColdwellM. A 100K well screen for a muscarinic receptor using the Epic® label-free system – a reflection on the benefits of the label-free approach to screening seven-transmembrane receptors. J. Recept. Signal Trans.29(3–4), 163–172 (2009).
  • Begley S , CarmichaelM. Desperately seeking cures.Newsweek. May 24 & 31, 38–42 (2010).
  • Rathore R , PribilP, CorrJJ, SeibelWL, EvdokimovA, GreisKD. Multiplex enzyme assays and inhibitor screening by mass spectrometry.J. Biomol. Screen.15(8), 1001–1007 (2010) (Epub).
  • Bowen BP , NorthenTR. Dealing with the unknown: metabolomics and metabolite atlases.J. Am. Soc. Mass. Spectrom.21(9), 1471–1476 (2010).
  • Young NL , Plazas-MayorcaMD, GarciaBA. Systems-wide proteomic characterization of combinatorial post-translational modification patterns.Expert Rev. Proteomics.7(1), 79–92 (2010).
  • Wang D , BodovitzS. Single cell analysis: the new frontier in ‘omics’.Trends Biotechnol.28(6), 281–290 (2010). (Epub).
  • Baxter MA , RoweC, AlderJet al. Generating hepatic cell lineages from pluripotent stem cells for drug toxicity screening. Stem Cell Res. 5(1), 4–22 (2010).
  • Murata M , TohyamaS, FukudaK. Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery.Pharmacol. Ther.126(2), 109–118 (2010).
  • Phillips BW , CrookJM. Pluripotent human stem cells: a novel tool in drug discovery.BioDrugs24(2), 99–108 (2010).
  • Sano Y , ShimizuF, AbeMet 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).
  • Gu Y , LiH, MikiJet 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).
  • Brandt S . TERT over-expression affects the growth of myocardial tissue derived from mouse embryonic stem cells.Differentiation,79(1), 1–8 (2010).
  • Cheung PY , DengW, ManCet al. Genetic alterations in a telomerase-immortalized human esophageal epithelial cell line: implications for carcinogenesis. Cancer Lett. 293(1), 41–51 (2010).
  • SRU Biosystems . Introducing the BIND® Scanner: low cell number applications in cytotoxicity, chemotaxis and differentiation. Presented at: SBS 16th Annual Conference & Exhibition, Phoenix, AZ, USA, 13April2010.
  • Huang WE , LiM, JarvisRM, GoodacreR, BanwartSA. Shining light on the microbial world the application of Raman microspectroscopy.Adv. Appl. Microbiol.70, 153–186 (2010).
  • Wachsmann-Hogiu S , WeeksT, HuserT. Chemical analysis in vivo and in vitro by Raman spectroscopy – from single cells to humans. Curr. Opin. Biotechnol.20(1), 63–73 (2009).
  • Bleicher KH , BöhmHJ, MüllerK, AlanineAI. Hit and lead generation: beyond high-throughput screening.Nat. Rev. Drug Discov.2(5), 369–378 (2003).
  • Keseru GM , MakaraGM. Hit discovery and hit-to-lead approaches.Drug Discov. Today11(15–16), 741–748 (2006).
  • Feng BY , ShoichetBK. Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures.J. Med. Chem.49(7), 2151–2154 (2006).
  • Jadhav A , FerreiraRS, KlumppCet al. Quantitative analyses of aggregation, autofluorescence and reactivity artifacts in a screen for inhibitors of a thiol protease. J. Med. Chem. 53(1), 37–51 (2010).

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