LPS2336, a New TREK-1 Channel Activator Identified by High Throughput Screening.

ABSTRACT: TWIK-related K+ (TREK-1) channels are involved in pain perception and their pharmacological activation has potential for pain relief. The development of new pharmacological tools to study these channels and enrich our knowledge of structure-activity relationships is therefore important. We optimized a high throughput screening method based on thallium flux monitoring for the detection of TREK-1 activators in chemical libraries. We screened 1040 compounds from the French National Essential Chemical Library and identified LPS2336 as a potent TREK-1 activator with an EC₅₀ of 11.76 µM. Thirty-three LPS2336 analogs were subsequently tested but none of them retained activity on TREK-1. In vivo, LPS2336 produces antinociceptive activity when administered systemically and, to a lesser e

SUBMITTER: Boyer R 

PROVIDER: S-EPMC12109561 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature