Yoda 1 is an agonist of the Piezo1 channel that agonizes human- and mouse-derived Piezo1 (EC50=17.1/26.6 μM). Yoda 1 is also an inhibitor of glycine transporter protein 2 (GlyT2).

Piezo1 (human, Piezo1-transfected HEK293T cells):26.6 μM, Piezo1 (Piezo1-transfected HEK293T cells):17.1 μM

METHODS: HEK293T cells transiently transfected with mouse and human Piezo1 and Piezo2 were treated with Yoda 1 (0-100 µM) and concentration response curves were examined by FLIPR.
RESULTS: Micromolar concentrations of Yoda1 induced a strong Ca2+ response in cells transfected with human or mouse Piezo1, but not in cells transfected with Piezo2, suggesting selectivity for Piezo1. The apparent EC50 of mouse and human Piezo1 was 17.1 µM and 26.6 µM, respectively.[1]
METHODS: HUVEC cells were cultured under laminar flow at a constant shear stress of 5dyn/cm2 or under static conditions of Yoda 1 (0.05-2 µM) for 24 h. The surface levels of ICAM-1 or VCAM-1 were measured by flow cytometry.
RESULTS: Incubation under constant shear stress increased surface expression of ICAM-1 by an average of 1.77±0.19-fold, but not VCAM-1. 24 h of Yoda 1 treatment mimicked this response, inducing a concentration-dependent increase in ICAM-1 surface expression. 1 µM Yoda 1 significantly increased ICAM-1 levels by 1.45±0.11-fold over the control, while VCAM-1 surface expression was unaffected. [2]

METHODS: To study the effects on osteoblasts, Yoda 1 (5 µmol/kg) was injected intraperitoneally into C57BL/6J mice five times per week for two weeks.
RESULTS: Yoda 1 did not alter body weight, but increased cortical thickness and cancellous bone mass in the distal femur. Yoda 1 also increased cortical thickness in the vertebrae, with no detectable change in cancellous bone volume in the vertebrae. Consistent with the effects on bone mass, serum osteocalcin (a marker of bone formation) levels were elevated in Yoda 1-treated mice. Yoda 1 activation of Piezo1 mimicked the effects of fluid shear stress on osteoblasts and increased bone mass in the mice. [3]