Chromenone derivatives as novel pharmacological chaperones for retinitis pigmentosa-linked rod opsin mutants.

ABSTRACT: The correct expression of folded, functional rhodopsin (Rho) is critical for visual perception. However, this seven-transmembrane helical G protein-coupled receptor is prone to mutations with pathological consequences of retinal degeneration in retinitis pigmentosa (RP) due to Rho misfolding. Pharmacological chaperones that stabilize the inherited Rho variants by assisting their folding and membrane targeting could slow the progression of RP. In this study, we employed virtual screening of synthetic compounds with a natural product scaffold in conjunction with in vitro and in vivo evaluations to discover a novel chromenone-containing small molecule with favorable pharmacological properties that stabilize rod opsin. This compound reversibly binds to unliganded bovine rod opsin with an EC50

SUBMITTER: Ortega JT 

PROVIDER: S-EPMC9558842 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature