Yoda2 (KC289)

Novel, selective Piezo1 channel activator which shows improved (or equivalent) reliability, efficacy and potency in functional assays compared to Yoda1 (EC₅₀ values are 150nM and 600nM at mouse Piezo1 in calcium assays for Yoda2 (KC289) and Yoda1 respectively). Selective for Piezo1 over other membrane proteins and suggested to have greater effect and potency at mouse Piezo1 compared to human Piezo1. Also shows improved aqueous solubility more suited to physiological conditions than those of Yoda1 (~160x more soluble in aqueous buffer than Yoda1). Active in vivo and shows vasorelaxant effects consistent with Piezo1 agonism. Recently shown to help promote cortical bone parameters in mice.

Soluble in DMSO (50 mM with warming)

When Parsonage et al used Yoda2 (KC289) in universal aqueous buffer, a final DMSO concentration of 0.5% was used to maintain solubility of the compound.

Meslier et al prepared working solutions in 0.9% (w/v) Sodium Chloride, 5% DMSO, and 10% (w/v) cyclodextrin SBE-B-CD, to facilitate solubilization of the compound.

4-(5-{[(2,6-dichlorophenyl)methyl]sulfanyl}-1,3,4-thiadiazol-2-yl)benzoic acid potassium salt

C₁₆H₉Cl₂KN₂O₂S₂