Cellular Dielectric Spectroscopy: A Label-Free Technology for Drug Discovery

SLAS Technology - Tập 10 - Trang 258-269 - 2005
Gordon Leung1, H. Roger Tang1, Ryan McGuinness1, Edward Verdonk1, Julia M. Michelotti1, Vivian F. Liu1
1MDS Sciex, South San Francisco, CA

Tóm tắt

Cellular dielectric spectroscopy (CDS) provides realtime, label-free, universal measurements, enabling comprehensive pharmacological evaluation of cell surface receptors in living cells. The sensitivity of the measurement allows monitoring of ligand-mediated activation of endogenous receptors, therefore generating physiologically relevant data. Activation of receptors results in CDS response profiles that are characteristic of main subsets of G-protein coupled receptors (GPCRs) within a cell line. This allows cluster analysis of response profiles that may be used in several important applications, which include identification of the G-protein coupling of orphan GPCRs and the cataloging of active endogenous receptors in cells. In this study, CDS technology is used in the pharmacological evaluation of multiple receptors in many cell types, including primary cells. Specifically, data is presented demonstrating hit confirmation, receptor selectivity analysis, ligand potency, and Schild analysis of receptor-selective antagonists. CDS results compare favorably to other cell-based assays, and the robustness and reproducibility of CDS assays are reflected by low assay coefficient of variation (CVs) and reliable Z'-scores of the data. Because CDS requires no stable or transiently transfected cells or special reagents, assay development and data acquisition is simple and fast. The ease of use, universality, and label-free nature of the CDS-based platform make it well suited to secondary screening applications in drug discovery.

Tài liệu tham khảo

Foster K., 1989, Crit. Rev. Biomed. Eng., 17, 25 10.1002/(SICI)1521-186X(1996)17:6<475::AID-BEM7>3.0.CO;2-0 10.1016/0302-4598(96)05066-0 Schwan H., 1993, Med. Prog. Technol., 19, 163 10.1016/S0006-3495(96)79420-1 10.1016/S1567-5394(01)00110-4 10.1016/S0022-3093(02)01111-0 10.1016/0302-4598(96)05064-7 10.1002/jps.2600840902 10.1016/0165-022X(96)00005-X 10.1016/S0006-3495(01)75746-3 10.1016/S0006-3495(01)75745-1 10.1016/S0006-3495(99)77191-2 10.1085/jgp.113.5.743 Tamada T., 2001, JOP, 2, 219 10.1172/JCI118493 10.1152/ajplung.2000.278.5.L888 10.1111/j.1469-7793.2001.0433a.x 10.1113/jphysiol.2001.013289 10.1007/BF02522485 10.1016/0956-5663(96)89087-7 10.1088/0031-9155/45/11/312 10.1021/ac0011585 10.1006/excr.2000.4919 10.1073/pnas.88.17.7896 Santini M., 1994, Exp Hematol, 22, 40 10.1016/S0956-5663(97)00045-6 10.1007/s004240050864 10.1096/fj.02-0096fje 10.1182/blood.V99.12.4466 10.1074/jbc.M204477200 10.1124/mol.61.2.277 10.1152/ajplung.2001.281.4.L824 10.1074/jbc.274.50.35944 10.1152/ajplung.2001.280.6.L1094 10.1016/S0898-6568(99)00012-1 Maddala R., 2003, Mol Vis, 9, 329 10.1002/cm.10171 10.1210/endo.137.11.8895334 10.1152/ajprenal.00331.2003 10.1111/j.1460-9568.2004.03845.x 10.1152/ajpcell.2001.281.5.C1468 10.1074/jbc.M106724200 10.1152/ajprenal.1997.273.2.F283 10.1083/jcb.106.6.1955 10.3109/10623320009072215 10.1016/S0898-6568(02)00087-6 Chuntharapai A., 1994, J Immunol, 153, 5682, 10.4049/jimmunol.153.12.5682 10.1182/blood.V90.11.4588 10.1111/j.1476-5381.1996.tb16705.x 10.1002/ijc.2910170504 Hebert C., 1991, J. Biol. Chem., 266, 18989, 10.1016/S0021-9258(18)55160-7 10.1074/jbc.273.17.10095 Hill P., 1996, Adv Neurol, 69, 41 10.1177/1087057104267788 Comley J., 2005, Drug Discovery World, 6, 63
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SLAS Technology

Tập 10

258-269

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