α-Conotoxin GeXIVA

α-Conotoxin GeXIVA (αO-conotoxin GeXIVA or GeXIVA) is a 28 amino acid peptidyl toxin, which was discovered from a transcriptome analysis of the South China Sea mollusk, Conus generalis¹. GeXIVA belongs to the O1-gene superfamily and is a potent and selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype¹. The toxin-mediated blockade of α9α10 nAChRs is voltage-dependent, suggesting that the toxin binding site might be allosterically coupled to a voltage-sensitive domain of the nAChR^1,2. GeXIVA exhibits analgesic activity in animal models of pain without the development of tolerance^1-4.

nAChRs are involved in a wide range of physiological functions in the central and peripheral nervous systems.  Alterations in nAChR expression and/or function are associated with a number of pathophysiological conditions including pain, addiction, epilepsy, autism, schizophrenia, Alzheimer's and Parkinson's diseases, as well as many types of cancers^2,6. The nAChRs are formed from the assembly of five homologous subunits and neuronal nAChRs are assembled from a combination of α- and β-subunits. They share a common basic structure, but their pharmacological and functional properties arise from the wide range of different subunit combinations which generate distinctive subtypes⁶. The α9α10 nAChR subtype is a potential target for treating chronic pain, wound healing, the pathophysiology of the auditory system, and various cancers^4-7. GeXIVA potently alleviated neuropathic pain in several rat models^1-4 and also exhibited an antitumor effect^5,8.