Analog conotoxins and similar peptides that block the α9α10 nicotinic acetylcholine receptor for the treatment of pain and inflammatory conditions.

The opioid epidemic continues to be a leading cause of accidental death in the United States with opioids contributing to over 70,000 overdose fatalities every year (roughly 130 people every day). While the risk of addiction and potential to overdose is well known, doctors and patients have limited alternatives to manage acute and chronic pain.

University of Utah researchers have developed a collection of peptides, including RgIA and other conotoxin peptides, that block the α9α10 subtype of the nicotinic acetylcholine receptor (nAChR) that plays a major role in chronic pain. These researchers have utilized a variety of medicinal chemistry techniques to increase the stability and potency of these peptides for a potential non-opioid pain management option.

Note: This technology is related to U-6463.

Pre-Clinical Validation

• Non-addictive pain management option based on highly selective inhibition of the α9α10 nAChRs (IC50 of 0.9 nM for RgIA-5524).
• Many of the peptides have shown improved chemical stability with significantly reduced degradation in serum.

Zheng N, et al (2021). Discovery of Methylene Thioacetal-Incorporated α-RgIA Analogues as Potent and Stable Antagonists of the Human α9α10 Nicotinic Acetylcholine Receptor for the Treatment of Neuropathic Pain. J Med Chem: 8, 64(13): 9513-9524. doi: 10.1021/acs.jmedchem.1c00802.

Gajewiak J, et al (2021). Selective Penicillamine Substitution Enables Development of a Potent Analgesic Peptide that Acts through a Non-Opioid-Based Mechanism. J Med Chem: 8, 64(13): 9271-9278. doi: 10.1021/acs.jmedchem.1c00512.

Huynh P, et al (2020). RgIA4 Accelerates Recovery from Paclitaxel-Induced Neuropathic Pain in Rats. Mar. Drugs: 18(1): 12. doi:10.3390/md18010012

Jason Young
(801) 587-0519
jason.r.young@utah.edu