Fig. 2: (R)-isosakuranetin – not (S)-isosakuranetin - is a potent TRPM3 antagonist.
From: Stereoselectivity and functional plasticity of a common ligand-binding pocket in TRPM3
a Cryo-EM density at the ligand binding site for isosakuranetin. (R)-isosakuranetin is shown in violet-purple and (S)-isosakuranetin in yellow. The density is contoured at a level of 8σ in pymol. The model-map fit values as calculated in ChimeraX are provided on the right. Chemical drawings for (R)- and (S)-isosakuranetin are indicated below the density. b Chiral HPLC showing two peaks in commercial isosakuranetin. c Normalized fluorescence traces showing changes in jRCAMP1b fluorescence in cells expressing WT human TRPM3, showing the effect of application of various concentrations of racemic isosakuranetin and its two enantiomers or vehicle (black traces) on responses evoked by PS. At the end of the experiment, a saturating ionomycin response was evoked for normalization. d Concentration-inhibition curves for racemic isosakuranetin and the two enantiomers. Each data point represents the mean ± SEM from 4 biological replicates (individual wells). Source data are provided as a Source Data file.
