Identification of potent and selective small molecule inhibitors of the cation channel TRPM4.

ABSTRACT:

Background and purpose

TRPM4 is a calcium-activated non-selective cation channel expressed in many tissues and implicated in several diseases, and has not yet been validated as a therapeutic target due to the lack of potent and selective inhibitors. We sought to discover a novel series of small-molecule inhibitors by combining in silico methods and cell-based screening assay, with sub-micromolar potency and improved selectivity from previously reported TRPM4 inhibitors.

Experimental approach

Here, we developed a high throughput screening compatible assay to record TRPM4-mediated Na⁺ influx in cells using a Na⁺ -sensitive dye and used this assay to screen a small set of compounds selected by ligand-based virtual screening using previously known weakly ac

SUBMITTER: Ozhathil LC 

PROVIDER: S-EPMC6002741 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature