生物活性

• 描述Piezo1 protein, encoded by PIEZO1 gene, is a mechanically-activated ion channel that links mechanical forces to biological signals. Piezo1 contains 36 transmembrane domains and functions as a homotetramer. Piezo1 plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling. Moreover, Piezo1 acts as shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation and it plays a key role in blood vessel formation and vascular structure in both development and adult physiology. GlyT2-IN-1, also termed 'Yoda-1', is an agonist for both human and mouse Piezo1, with EC50 values of 26.6 μM and 17.1μM for human and mouse Piezo1, respectively^[3]. In HEK293T cells transiently transfected with mouse Piezo1, Yoda-1 mediated Ca2+ responses at the concentration of 25 μM, and this effect depended on calcium influx as the chelation of extracellular calcium dramatically reduced the responses and the depletion of intracellular calcium stores did not. Also in mouse Piezo1 transfected HEK293T cells, using a cell attached patch configuration, it was measured that Yoda-1 notably slowed the inactivation phase of the transient currents at the concentration of 30 μM. Utilizing artificial droplet lipid bilayers, it was shown that Yoda-1 activated purified Piezo1 channels in the absence of other cellular components at the concentration of 1 μM^[3].

• 动物研究
  剂量	Mice: 0.4 mg/kg[3] (duct injection, 5 µL/min for 10 min)
  给药途径	Duct injection

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03146923	Renal Dialysis ... more >> Hyperphosphatemia Dietary Modification Collapse <<	Not Applicable	Completed	-	Ireland ... more >> Midland Regional Hospital Tullamore Tullamore, Offaly, Ireland, R35 NY51 Cavan General Hospital Cavan, Ireland, H12 K845 Fiona Byrne Cork, Ireland, T12DC4A St. Vincents University Hospital Dublin, Ireland, D04 T6F4 Mater Misericordia University Hospital Dublin, Ireland, D07 R2WY Beaumont Hospital Dublin, Ireland, D09 C562 Tallaght Hospital Dublin, Ireland, D24 NR0A Galway University Hospitals Galway, Ireland University Hospital Limerick Limerick, Ireland, V94 F858 Mayo University Hospital Mayo, Ireland, F23 H529 Collapse <<
  NCT03510468	Healthy Volunteers	Phase 1	Recruiting	August 30, 2021	United States, Maryland ... more >> National Institutes of Health Clinical Center Recruiting Bethesda, Maryland, United States, 20892 Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov Collapse <<
  NCT02647723	Pregnancy Chi... more >>ld Development Collapse <<	Not Applicable	Recruiting	April 2020	United States, Illinois ... more >> University of Chicago Medicine Recruiting Chicago, Illinois, United States, 60637 Contact: Kimberley R Mbayiwa, MA    773-702-2670    kmbayiwa@bsd.uchicago.edu Collapse <<

• 参考文献

• [1] Syeda R, Xu J, Dubin AE, et al. Chemical activation of the mechanotransduction channel Piezo1. Elife. 2015

  [2] Mikhailov N, Leskinen J, Fagerlund I, et al. Mechanosensitive meningeal nociception via Piezo channels: Implications for pulsatile pain in migraine?. Neuropharmacology. 2019

  [3] Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, Lao J, Tully DC, Engels IH, Petrassi HM, Schumacher AM, Montal M, Bandell M, Patapoutian A. Chemical activation of the mechanotransduction channel Piezo1. Elife. 2015 May 22;4:e07369.