Huwentoxin-IV (TFA)

Huwentoxin-IV TFA is a potent and selective sodium channel blocker, inhibits neuronal Nav1.7, Nav1.2, Nav1.3 and Nav1.4 with IC50s of 26, 150, 338 and 400 nM, respectively. Huwentoxin-IV TFA preferentially blocks peripheral nerve subtype Nav1.7 by binding neurotoxin receptor site 4. Huwentoxin-IV TFA has analgesic effects on animal models of inflammatory and neuropathic pain[1][2].

O=C(N[C@@H](CSSC[C@@H](C(N[C@@H](CCCCN)C(N[C@@H](CO)C(N[C@@H](CO)C(N[C@@H](CCCCN)C(N[C@@H](CC(C)C)C(N[C@H]1C(C)C)=O)=O)=O)=O)=O)=O)NC2=O)C(N[C@@H](CC(C)C)C(N[C@@H](CCC(O)=O)C(N[C@@H]([C@@H](C)CC)C(N[C@@H](CC3=CC=CC=C3)C(N[C@@H](CCCCN)C(N[C@@H](C)C(N[C@@H](CSSC[C@@H](C(N[C@@H](CO)C(N[C@@H](CCCNC(N)=N)C(N[C@@H](CCCCN)C(N[C@@H]([C@H](O)C)C(N[C@@H](CCCNC(N)=N)C(N[C@H]4CC5=CNC6=CC=CC=C56)=O)=O)=O)=O)=O)=O)NC1=O)C(N[C@@H](CC(N)=O)C(N7[C@@H](CCC7)C(N[C@@H](CO)C(N[C@@H](CC(N)=O)C(N[C@@H](CC(O)=O)C(N[C@@H](CCC(N)=O)C(N[C@H]2CSSC[C@@H](C(N[C@@H](CCCCN)C(N[C@@H](CC8=CC=C(C=C8)O)C(N[C@@H](CCC(N)=O)C(N[C@@H]([C@@H](C)CC)C(N)=O)=O)=O)=O)=O)NC4=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)[C@H](CCC(O)=O)N.O=C(O)C(F)(F)F.[x]

[1]Liu Y, et, al. Analgesic effects of Huwentoxin-IV on animal models of inflammatory and neuropathic pain. Protein Pept Lett. 2014; 21(2): 153-8.|[2]Xiao Y, et, al. Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. J Biol Chem. 2008 Oct 3;283(40):27300-13.