Abstract
It has been estimated that over a billion dollars in resources can be consumed to obtain clinical approval, and only a few new chemical entities are approved by the US Food and Drug Administration (FDA) each year. Therefore it is of utmost importance to obtain the maximum amount of information about biological activity, toxicological profile, biochemical mechanisms, and off-target interactions of drug-candidate leads in the earliest stages of drug discovery. Cell-based assays, because of their peculiar advantages of predictability, possibility of automation, multiplexing, and miniaturization, seem the most appealing tool for the high demands of the early stages of the drug-discovery process. Nevertheless, cellular screening, relying on different strategies ranging from reporter gene technology to protein fragment complementation assays, still presents a variety of challenges. This review focuses on main advantages and limitations of different cell-based approaches, and future directions and trends in this fascinating field.
Similar content being viewed by others
References
Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindborg SR, Schacht AL (2010) Nat Rev Drug Discov 9:203–214
Weigelt J (2009) EMBO 10:941–945
Chan JN, Nislow C, Emili A (2010) Trends Pharmacol Sci 31:82–88
Shou WZ, Zhang J (2010) Expert Opin Drug Metab Toxicol 6:321–336
Kieltyka K, Zhang J, Li S, Vath M, Baglieri C, Ferraro C, Zvyaga TA, Drexler DM, Weller HN, Shou WZ (2009) Rapid Commun Mass Spectrom 23:1579–1591
Banerjee P, Bhunia AK (2009) Trends Biotechnol 27:179–188
Wu MH, Huang SB, Lee GB (2010) Lab Chip 10:939–956
De A, Ray P, Loening AM, Gambhir SS (2009) FASEB J 23:2702–2709
Bacart J, Corbel C, Jockers R, Bach S, Couturier C (2008) Biotechnol J 3:311–324
Kamal M, Marquez M, Vauthier V, Leloire A, Froguel P, Jockers R, Couturier C (2009) Biotechnol J 4:1337–1344
Misawa N, Kafi AK, Hattori M, Miura K, Masuda K, Ozawa T (2010) Anal Chem 82:2552–2560
Zanella F, Lorens JB, Link W (2010) Trends Biotechnol 28:237–245
Roda A, Pasini P, Mirasoli M, Michelini E, Guardigli M (2004) Trends Biotechnol 22:295–303
Wolff M, Kredel S, Wiedenmann J, Nienhaus GU, Heilker R (2008) Comb Chem High Throughput Screen 11:602–609
Fan F, Wood KV (2007) Assay Drug Dev Technol 5:127–136
Branchini BR, Southworth TL, Khattak NF, Michelini E, Roda A (2005) Anal Biochem 345:140–148
Ilagan RP, Rhoades E, Gruber DF, Kao HT, Pieribone VA, Regan L (2010) FEBS J 277:1967–1978
Sellix MT, Currie J, Menaker M, Wijnen H (2010) J Biol Rhythms 25:228–232
Ullmann K, Wiencierz AM, Müller C, Thierbach R, Steege A, Toyokuni S, Steinberg P (2008) Free Radic Res 42:746–753
Yang Y, Zhang Z, Jiang W, Gao L, Zhao G, Zheng Z, Wang M, Si S, Hong B (2007) J Biomol Screen 12:211–219
Cali JJ, Niles A, Valley MP, O'Brien MA, Riss TL, Shultz J (2008) Expert Opin Drug Metab Toxicol 4:103–120
Lim HK, Duczak N Jr, Brougham L, Elliot M, Patel K, Chan K (2005) Drug Metab Dispos 33:1211–1219
Sinz M, Wallace G, Sahi J (2008) AAPS J 10:391–400
Zhu Z, Puglisi J, Connors D, Stewart J, Herbst J, Marino A, Sinz M, O'Connell J, Banks M, Dickinson K, Cacace A (2007) J Biomol Screen 12:248–254
Fuentes G, Oyarzabal J, Rojas AM (2009) Curr Opin Drug Discov Dev 12:358–366
Roda A, Guardigli M, Michelini E, Mirasoli M (2009) Anal Bioanal Chem 393:109–123
Yu X, Sainz B Jr, Uprichard SL (2009) Antimicrob Agents Chemother 53:4311–4319
Hwang YC, Chu JJ, Yang PL, Chen W, Yates MV (2008) Antiviral Res 77:232–236
Hamdan FF, Audet M, Garneau P, Pelletier J, Bouvier M (2005) J Biomol Screen 10:463–475
Mazars A, Fåhraeus R (2010) Biotechnol J 5:377–384
Koterba KL, Rowan BG (2006) Nucl Recept Signal 4:e021
De A, Ray P, Loening AM, Gambhir SS (2007) Cancer Res 67:7175–7183
De A, Ray P, Loening AM, Gambhir SS (2009) FASEB J 23:2702–2729
Pfleger KD, Dromey JR, Dalrymple MB, Lim EM, Thomas WG, Eidne KA (2006) Cell Signal 18:1664–1670
Carriba P, Navarro G, Ciruela F, Ferré S, Casadó V, Agnati L, Cortés A, Mallol J, Fuxe K, Canela EI, Lluís C, Franco R (2008) Nat Methods 5:727–733
Ozawa T, Yakugaku Z (2009) 129:289–295
Kim SB, Takao R, Ozawa T, Umezawa Y (2005) Anal Chem 77:6928–6934
Kaihara A, Umezawa Y (2008) Chem Asian J 3:38–45
Chan CT, Paulmurugan R, Gheysens OS, Kim J, Chiosis G, Gambhir SS (2008) Cancer Res 68:216–226
Paulmurugan R, Gambhir SS (2006) Proc Natl Acad Sci USA 103:15883–15888
Paulmurugan R, Gambhir SS (2005) Anal Chem 77:1295–1302
Paulmurugan R, Gambhir SS (2007) Anal Chem 79:2346–2353
Luker KE, Piwnica-Worms D (2004) Methods Enzymol 385:349–360
Luker KE, Gupta M, Luker GD (2008) Anal Chem 80:5565–5573
Luker KE, Gupta M, Luker GD (2009) FASEB J 23:823–834
Villalobos V, Naik S, Piwnica-Worms D (2008) Methods Mol Biol 439:339–352
Chan CT, Paulmurugan R, Reeves RE, Solow-Cordero D, Gambhir SS (2009) Mol Imaging Biol 11:144–158
Remy I, Michnick SW (2006) Nat Methods 3:977–979
Kim SB, Sato M, Tao H (2009) Anal Chem 81:67–74
Kim SB, Umezawa Y, Kanno KA, Tao H (2008) ACS Chem Biol 3:359–372
Kanno A, Yamanaka Y, Hirano H, Umezawa Y, Ozawa T (2007) Angew Chem Int Ed Engl 46:7595–7599
Brough SJ, Shah P (2009) Methods Mol Biol 552:181–198
Rowe L, Ensor M, Mehl R, Daunert S (2010) ACS Chem Biol. In press, 10.1021/cb9002909
Drobac E, Tricoire L, Chaffotte AF, Guiot E, Lambolez B (2010) J Neurosci Res 88:695–711
Abbitt KB, Rainger GE, Nash GB (2000) J Immunol Methods 239:109–119
Xi B, Yu N, Wang X, Xu X, Abassi YA (2008) Biotechnol J 3:484–495
Peters MF, Vaillancourt F, Heroux M, Valiquette M, Scott CW (2010) Assay Drug Dev Technol 8:219–227
McGuinness RP, Proctor JM, Gallant DL, van Staden CJ, Ly JT, Tang FL, Lee PH (2009) Comb Chem High Throughput Screen 12:812–823
Fang Y, Frutos AG, Verklereen R (2008) Comb Chem High Throughput Screen 11:357–369
Hug TS, Prenosil JE, Morbidelli M (2001) Biosens Bioelectron 16:865–874
Endo T, Yamamura S, Kerman K, Tamiya E (2008) Anal Chim Acta 614:182–189
Minor LK (2008) Comb Chem High Throughput Screen 11:573–580
Verdonk E, Johnson K, McGuinness R, Leung G, Chen YW, Tang HR, Michelotti JM, Liu VF (2006) Assay Drug Dev Technol 4:609–619
Marx KA, Zhou T, Montrone A, McIntosh D, Braunhut SJ (2007) Anal Biochem 361:77–92
Marx KA, Zhou T, Montrone A, Schulze H, Braunhut SJ (2001) Biosens Bioelectron 16:773–782
Liu Q, Yu J, Xiao L, Tang JC, Zhang Y, Wang P, Yang M (2009) Biosens Bioelectron 24:1305–1310
Arias LR, Perry CA, Yang L (2010) Biosens Bioelectron. 25:2225–31
Lee R, Kim PH, Choi JW, Oh-Joon K, Kim K, Kim D, Yun CO, Yoo KH (2010) Biosens Bioelectron 25:1325–1332
Asphahani F, Zhang M (2007) Analyst 132:835–841
McGuinness R (2009) Assay Drug Dev Technol 7:191–193
Wlodkowic D, Cooper JM (2010) Anal Bioanal Chem. doi:10.1007/s00216-010-3722-8
Soikkeli A, Sempio C, Kaukonen AM, Urtti A, Hirvonen J, Yliperttula M (2010) J Biomol Screen 15:30–41
Wunder F, Kalthof B, Müller T, Hüser J (2008) Comb Chem High Throughput Screen 11:495–504
Bergsdorf C, Kropp-Goerkis C, Kaehler I, Ketscher L, Boemer U, Parczyk K, Bader B (2008) Assay Drug Dev Technol 6:39–53
An WF, Tolliday N (2010) Mol Biotechnol 45:180–186
Li CW, Yang J, Yang M (2006) Lab Chip 6:921–929
Liu D, Wang L, Zhong R, Li B, Ye N, Liu X, Lin B (2007) J Biotechnol 131:286–292
Di L, Kerns EH (2006) Drug Discov Today 11:446–451
Grant RJ, Roberts K, Pointon C, Hodgson C, Womersley L, Jones DC, Tang E (2009) J Biomol Screen 14:452–459
Joelsson D, Gates IV, Pacchione D, Wang CJ, Bennett PS, Zhang Y, McMackin J, Frey T, Brodbeck KC, Baxter H, Barmat SL, Benetti L, Bodmer JL (2010) J Virol Methods. 166:1–11
Upadhyaya S, Selvaganapathy PR (2010) Lab Chip 10:341–348
Niles AL, Moravec RA, Riss TL (2009) Curr Chem Genomics 3:33–41
Nakanishi J, Takarada T, Yamaguchi K, Maeda M (2008) Anal Sci 24:67–72
Gan J, Chen H, Zhou F, Huang H, Zheng J, Song W, Yuan L, Wu Z (2010) Colloids Surf B 76:381–385
Qin D, Xia Y, Whitesides GM (2010) Nat Protoc 5:491–502
Zawko SA, Schmidt CE (2010) Lab Chip 10:379–383
Murugan R, Molnar P, Rao KP, Hickman JJ (2009) Int J Biomed Eng Technol 2:104–134
Park TH, Shuler ML (2003) Biotechnol Prog 19:243–253
Frimat JP, Sisnaiske J, Subbiah S, Menne H, Godoy P, Lampen P, Leist M, Franzke J, Hengstler JG, van Thriel C, West J (2010) Lab Chip 10:701–709
Asphahani F, Thein M, Veiseh O, Edmondson D, Kosai R, Veiseh M, Xu J, Zhang M (2008) Biosens Bioelectron 23:1307–1313
Pampaloni F, Reynaud EG, Stelzer EH (2007) Nat Rev Mol Cell Biol 8:839–845
Kogashiwa Y, Sakurai H, Kimura T, Kohno N (2010) Canc Sci. In press, doi:10.1111/j.1349-7006.2010.01540
Vaira V, Fedele G, Pyne S, Fasoli E, Zadra G, Bailey D, Snyder E, Faversani A, Coggi G, Flavin R, Bosari S, Loda M (2010) Proc Natl Acad Sci USA. 107:8352–6
Park JH, Chung BG, Lee WG, Kim J, Brigham MD, Shim J, Lee S, Hwang CM, Durmus NG, Demirci U, Khademhosseini A (2010) Biotechnol Bioeng 106:138–148
El-Said WA, Yea CH, Kim H, Oh BK, Choi JW (2009) Biosens Bioelectron 24:1259–1265
Liu T, Lin B, Qin J (2010) Lab Chip. In press,doi:10.1039/c000022a
Herbst J, Anthony M, Stewart J, Connors D, Chen T, Banks M, Petrillo EW, Agler M (2009) Assay Drug Dev Technol 7:294–303
Nakajima Y, Kimura T, Sugata K, Enomoto T, Asakawa A, Kubota H (2005) Biotechniques 38:891–894
Michelini E, Cevenini L, Mezzanotte L, Ablamsky D, Southworth T, Branchini B, Roda A (2008) Anal Chem 80:260–267
Chin J, Adams AD, Bouffard A, Green A, Lacson RG, Smith T, Fischer PA, Menke JG, Sparrow CP, Mitnaul LJ (2003) Assay Drug Dev Technol 1:777–787
Marine S, Zamiara E, Smith ST, Stec EM, McGarvey J, Kornienko O, Jiang G, Wong KK, Stack JH, Zhang BB, Ferrer M, Strulovici B (2006) Anal Biochem 355:267–277
Brandish PE, Chiu CS, Schneeweis J, Brandon NJ, Leech CL, Kornienko O, Scolnick EM, Strulovici B, Zheng W (2006) J Biomol Screen 11:481–487
Patel A, Murray J, McElwee-Whitmer S, Bai C, Kunapuli P, Johnson EN (2009) Anal Biochem 385:286–292
Walker GM, Ozers MS, Beebe DJ (2002) Biomed Microdevices 4:161–166
Yu HM, Alexander CM, Beebe DJ (2007) Lab Chip 7:726–730
Paguirigan AL, Beebe DJ (2009) Integr Biol (Camb) 1:182–195
McLeod HL (2010) Heart Fail Rev 15:183–185
Akkari PA, Swanson TW, Crenshaw DG, Grossman I, Sundseth S, Burns DK, Roses AD (2009) Curr Pharm Des 15:3754–3763
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Michelini, E., Cevenini, L., Mezzanotte, L. et al. Cell-based assays: fuelling drug discovery. Anal Bioanal Chem 398, 227–238 (2010). https://doi.org/10.1007/s00216-010-3933-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-010-3933-z