High-Throughput Screening of Na(V)1.7 Modulators Using a Giga-Seal Automated Patch Clamp Instrument

Area of Science:

• Neuroscience
• Pharmacology
• Biophysics

Background:

• Voltage-gated sodium (Na(V)) channels, particularly Na(V)1.7, are crucial for pain sensation.
• Developing Na(V)1.7 inhibitors for pain treatment remains a significant challenge.
• Novel high-throughput screening (HTS) technologies are needed to expedite ion channel drug discovery.

Purpose of the Study:

• To evaluate the Sophion Qube, a next-generation automated patch clamp (APC) platform, for high-throughput screening of Na(V)1.7 modulators.
• To assess the instrument's performance in a large-scale compound screen and validate its IC50 assay capabilities.
• To determine if the Qube can accelerate the hit-to-lead process in ion channel drug discovery.

Main Methods:

• A Na(V)1.7 HTS campaign was conducted using the Sophion Qube, testing 158,000 compounds from Pfizer's compound library.
• IC50 assay validation and protocol optimization were performed using reference compounds.
• Data generated on the Qube were compared with results from the established Sophion QPatch APC platform.

Main Results:

• The Qube demonstrated a high median success rate of 83% in the large-scale APC screening.
• The instrument successfully generated IC50 potency data, showing correlation with the QPatch platform.
• The Qube proved capable of testing thousands of compounds per day, significantly increasing throughput.

Conclusions:

• The Sophion Qube offers a robust, reliable, and significantly faster APC assay for screening Na(V)1.7 modulators.
• This technology has the potential to accelerate the identification and lead optimization of novel pain therapeutics.
• The Qube platform facilitates efficient drug discovery for ion channels involved in pain pathways.