Yoda1

Yoda1 (CAS No.: 448947-81-7) is a small-molecule, selective agonist of the mechanosensitive ion channel Piezo1, widely used as a chemical probe to investigate mechanotransduction and calcium signaling in biomedical research. It directly activates purified and heterologously expressed Piezo1 channels and exhibits functional activity in the low micromolar range, with reported EC50 values in the tens of micromolar for both murine and human Piezo1 systems, while showing selectivity over closely related Piezo2 channels. Mechanistically, Yoda1 enhances calcium influx through Piezo1, prolongs channel open states by slowing inactivation kinetics, and increases channel sensitivity to mechanical stimuli, thereby lowering the pressure threshold required for activation. Downstream effects include activation of calcium-dependent potassium channels such as KCa3.1 and suppression of Rac1 signaling, as well as inhibition of epidermal growth factor-induced macropinocytosis. In cellular models, Yoda1 has been shown to induce pronounced physiological responses, including alterations in red blood cell morphology and hydration status in a Piezo1-dependent manner. This compound is broadly applied in studies of vascular biology, red blood cell physiology, cancer cell uptake pathways, and ion channel pharmacology, as well as in drug discovery efforts targeting mechanosensitive pathways. Experimental concentrations and treatment regimens vary depending on the specific cellular context, assay design, and research objectives.