Cryo-EM structure enabling virtual screening for the discovery of highly potent TRPM3 antagonists with analgesic efficacy - PubMed
3 hours ago
- #cryo-EM
- #TRPM3
- #analgesia
- Current analgesics have limitations in efficacy and adverse effects.
- TRPM3 is a non-opioid target in sensory neurons with therapeutic potential.
- Lack of potent, selective TRPM3 antagonists and unresolved structural pharmacology pose challenges.
- Cryo-EM structures of human TRPM3 revealed a compact ligand-binding pocket.
- Virtual screening enabled discovery of a picomolar antagonist with favorable drug-like properties.
- The antagonist showed potent, dose-dependent analgesia in rodent models of neuropathic and migraine pain.
- The study provides a structure-based discovery pipeline for TRP channels and validates TRPM3 as a therapeutic target.