High-throughput screening for ion channel modulators.
Ion channels present a group of targets for major clinical indications, which have been difficult to address due to the lack of suitable rapid but biologically significant methodologies. To address the need for increased throughput in primary screening, the authors have set up a Beckman/Sagian core system to fully automate functional fluorescence-based assays that measure ion channel function. They apply voltage-sensitive fluorescent probes, and the activity of channels is monitored using Aurora's Voltage/Ion Probe Reader (VIPR). The system provides a platform for fully automated high-throughput screening as well as pharmacological characterization of ion channel modulators. The application of voltage-sensitive fluorescence dyes coupled with fluorescence resonance energy transfer is the basis of robust assays, which can be adapted to the study of a variety of ion channels to screen for both inhibitors and activators of voltage-gated and other ion channels.
Falconer
Margaret
M
Lead Discovery Technologies, Pfizer Global Research and Development, Sandwich, United Kingdom.
Smith
Fiona
F
Surah-Narwal
Sandha
S
Congrave
Gill
G
Liu
Zhen
Z
Hayter
Paul
P
Ciaramella
Giuseppe
G
Keighley
Wilma
W
Haddock
Peter
P
Waldron
Gareth
G
Sewing
Andreas
A
D001331:Automation; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D015203:Reproducibility of Results
D005456:Fluorescent Dyes; D007473:Ion Channels