A FLIPR-Based HTS Assay to Identify N-Type Calcium Channel (CaV2.2) State-Dependent Blockers

SLAS, Orlando, FL, USA
January 15, 2013

CaV2.2 channels regulate neurotransmitter release in neurons and play a critical role in pain signaling. It has been proposed that a state-dependent CaV2.2 inhibitor which preferentially binds to channels in open or inactivated states may improve the therapeutic window over relatively state-independent CaV2.2 inhibitors. We have developed a robust fluorescent-based functional assay to identify state-dependent CaV2.2 inhibitors.
The novel assay design, coupled with an information-rich readout and sophisticated data analysis, led to a robust and reproducible identification of potent state-dependent CaV2.2 inhibitors, at a HTS-compatible throughput of ~10,000 compounds in 8 hours. The identified novel inhibitors will provide further insights and potentially therapeutic application regarding the role of CaV2.2 channels in pain.