Voltage-gated sodium channel inhibitor. It is unclear if it selectively inhibits Nav1.7/SCN9A or shows similar potency on all sodium channels tested (Ref.1, PubMed:31234412, PubMed:31443554). According to Escoubas et al., 2006 and Nicolas et al., 2019, it is selective over Nav1.7/SCN9A (90% inhibition at 1 uM), versus Nav1.4 and Nav1.6 (35% inhibition), and shows a small inhibition on all other sodium channels (except Nav1.8/SCN10A) (Ref.1, PubMed:31234412). According to Goncalves et al., 2019, it shows a similar inhibition on almost all sodium channels tested (Nav1.1/SCN1A (IC(50)=280.3 nM), Nav1.2/SCN2A (IC(50)=73.7 nM), Nav1.3/SCN3A (IC(50)=201.5 nM), Nav1.4/SCN4A (IC(50)>2100 nM), Nav1.5/SCN5A (IC(50)=710.6 nM), Nav1.6/SCN8A (IC(50)=491.2 nM), and Nav1.7/SCN9A (IC(50)=254.3-260 nM)), except Nav1.8/SCN10A (PubMed:31443554). The voltage-dependence of steady-state Nav1.7/SCN9A channel activation and inactivation are not affected, suggesting that is does not act as a gating-modifier toxin but rather blocks or impedes ion flux through the channel pore (Ref.1, PubMed:31234412). The toxin effect is partial and poorly reversible (PubMed:31234412). In addition to its inhibition to sodium channels, it also shows a small inhibition on rat Kv3.4/KCNC4 potassium channels (20% inhibition at 1 uM) (PubMed:31234412). In vivo, when tested on pain models, it shows analgesic activity (PubMed:31234412, PubMed:31443554). Expressed by the venom gland. The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin. This toxin may represent a lead for the development of novel analgesic agents. When injected into mice with an opioid analgesic drug and/or an enkephalinase inhibitor, it provides an enhanced and effective therapeutic approach to the treatment and/or prevention of pain (PubMed:28106092, Ref.2). When tested on the OD1-induced mouse model of Nav1.7/SCN9A-mediated pain, it almost completely reverses the induced pain (PubMed:31443554). In addition, it reduces the response of mice in both the acute pain and inflammation phases induced upon formalin injection into the paw (PubMed:31234412). Synthesis and folding of this linear peptide generates 4 peaks. Only the peak 1 shows a strong activity against Nav1.7/SCN9A. When analyzed in details, this peak shows two forms (P1' and P1''), which may be explained by the involvement of at least one Pro residue in a cis-trans isomerization. Does not show inhibition on mKv1.1/KCNA1, rKv1.2/KCNA2, rKv1.3/KCNA3, rKv1.4/KCNA4, mKv1.5/KCNA5, rKv1.6/KCNA6, rKv2.1, rKv2.2/KCNB2, rKv3.1/KCNC1, rKv3.2/KCNC2, mKv4.1/KCND1, rKv4.2/KCND2, dog Kv4.3/KCND3, KT3.1/KCNK3, rKir1.1/KCNJ1, mKir2.3/KCNJ4 (PubMed:31234412). Shows no or weak activity on Cav1.2/CACNA1C (IC(50)=5.9 uM), Kv11.1/KCNH2/ERG1/HERG (IC(50)>10 uM), and Nav1.8/SCN10A (IC(50)>10 uM) (PubMed:31443554). Belongs to the neurotoxin 10 (Hwtx-1) family.