Veragranine A analogs with improved synthetic efficiency and enhanced potency for the treatment of pain.
Chronic pain affects an estimated 20–30% of the global population, resulting in reduced quality of life, substantial economic costs, and increased reliance on opioid-based therapies. Although opioids remain a standard treatment for chronic pain, currently available pain management options often have limited efficacy and are associated with significant risks, including addiction, overdose, respiratory depression, constipation, and nausea. As a result, there is a need for safer, more effective non-opioid pain therapies that can provide meaningful pain relief while minimizing adverse effects. In parallel, improved synthetic methods are needed to enable efficient production of Veragranine A and its analogs for therapeutic development. These unmet needs create an opportunity for novel, potent, and scalable non-opioid analgesics to address a large and growing pain management market.
Inventors at Emory University have developed a new approach to synthesize over 200 mg of Veragranine A. This approach has also resulted in the synthesis of several new synthetic analogs that have shown greater efficacy in reducing pain in animal through modulation of voltage-gated ion channels, including calcium channels and, for select analogs, sodium channel activity, validated targets for non-addictive pain therapies. Together, these advances address both the need for scalable production and the development of more effective non-opioid analgesics for pain management.
Both in vitro and in vivo results are available.
Publication
Ma, D., Duran, P., Al-Ahmad, R., Hestehave, S., Joa, M., Alsbiei, O., Rodríguez-Palma, E. J., Li, Y., Wang, S., Khanna, R., & Dai, M. (2024). C–H functionalization-enabled 11-step semisynthesis of (−)-veragranine A and characterization of synthetic analogs in osteoarthritis-related pain treatment. Journal of the American Chemical Society, 146(24), 16698–16705. https://doi.org/10.1021/jacs.4c04025