protoxin-I

Protoxin-I (ProTx-I) is a 35-amino acid peptide toxin originally isolated from the venom of the Peruvian green velvet tarantula (*Thrixopelma pruriens*). It belongs to the inhibitory cystine knot (ICK) family of peptides. ProTx-I acts as a potent, non-selective inhibitor of various voltage-gated sodium (Nav) channels, including Nav1.1, Nav1.2, Nav1.5, Nav1.7, and Nav1.8. It functions as a gating modifier by binding to the voltage-sensor domains (VSDs) of these channels, specifically shifting the voltage dependence of activation toward more depolarized potentials. In addition to sodium channels, ProTx-I has been shown to inhibit T-type voltage-gated calcium channels (Cav3.1). Although primarily used as a high-affinity pharmacological tool in research, it is studied for its potential to inhibit metastasis in sodium-regulated cancers and its role in modulating nociceptive signaling for pain management.

Other names

Thrixopelma pruriens toxin 1Spider toxin ProTx-I