Description:
- Novel small-molecule Piezo1 agonists with high selectivity, strong metabolic stability, and minimal CYP450 interactions
- Enhances cerebrospinal fluid and lymphatic drainage through activation of Akt and eNOS signaling pathways
- Demonstrated reduction of ventricular fluid accumulation in hydrocephalus animal models, supporting therapeutic potential for neurological and lymphatic disorders
Abstract
This technology introduces novel Piezo1 calcium channel agonists that regulate fluid and lymphatic balance. Three structural classes, synthesized via nucleophilic substitution and Suzuki coupling, were confirmed by ^1H-NMR and LC-MS. Among 189 compounds, #12 showed strong Akt and eNOS activation, improved metabolic stability, Piezo1 selectivity, and reduced ventricular fluid in hydrocephalus models, highlighting its therapeutic and drug-development potential.
Benefit
- Potent and selective Piezo1 activation with strong metabolic stability and minimal CYP450 interaction
- Verified activation of Akt and eNOS pathways that improve CSF and lymphatic drainage, including enhanced toxin clearance when combined with focused ultrasound
- In vivo reduction of ventricular fluid buildup in hydrocephalus models
Market Application
- Alzheimer's and Parkinson’s Diseases, Glaucoma, Lymphedema
- Potential skin care by clearing reactive oxygen species
Publications
Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation, Nature Neuroscience, March 25, 2024.
Other
- Proof of concept studies completed.
- Small animal preclinical studies are ongoing.