Application:
- TRPA1 and TRPV1 are key peripheral ion channels involved in pain signaling and nociception.
- Although both channels interact with lipophilic ligands, the molecular basis of their interaction with cannabinoids is not fully understood.
- Natural cannabinoids such as CBD and CBG strongly activate TRPA1 but show weak and inconsistent activation of TRPV1.
- This lack of coordinated channel modulation limits the development of effective peripheral analgesics.
- A better understanding of lipid-sensing mechanisms is needed to enable rational drug design.
Our innovation:
- We developed a modified cannabinoid compound based on CBD and CBG using a structure-guided design approach.
- Introduction of the modifying moiety enables potent activation of both TRPA1 and TRPV1.
- The compounds activate TRPA1 via the cannabinoid-binding site and TRPV1 via the vanilloid-binding site.
- Dual activity was demonstrated in recombinant systems and primary sensory neurons.
- Binding mechanisms were validated using site-directed mutagenesis and molecular docking.
Advantages:
- Single chemical scaffold targeting two key pain channels
- Significantly enhanced potency and efficacy versus parent cannabinoids
- Mechanistically validated engagement of canonical binding sites
- Rational design framework for TRP channel modulation
- Identifies the carbamate group as a versatile chemical anchor
Opportunity:
- We are seeking collaboration with pharmaceutical and biotech companies developing pain and analgesic therapeutics to advance these compounds toward preclinical development.
- Potential collaborations include lead optimization and pharmacological evaluation for peripheral pain indications.
