Overview
Cys34 = C-terminal amidation
The product is soluble in pure water at high micromolar concentrations (100 µM - 1 mM). For long-term storage in solution, we recommend preparing a stock solution by dissolving the product in double-distilled water (ddH2O) at a concentration between 100-1000x of the final working concentration. Divide the stock solution into small aliquots and store at -20°C. Before use, thaw the relevant vial(s) and dilute to the desired working concentration in your working buffer.
Centrifuge all product preparations before use. It is recommended to prepare fresh solutions in working buffers just before use. Avoid multiple freeze-thaw cycles to maintain biological activity.
HsTX1[R14A] is an analogue of HsTX1, a 34-residue peptide toxin originally derived from the venom of the scorpion Heterometrus spinifer1,2. In this analogue, arginine at position 14 is substituted with alanine, resulting in a potent and selective blocker of voltage-gated potassium channels (KV1.3), with an IC50 of 45 ± 3 pM. HsTX1[R14A] exhibits more than 2,000-fold selectivity for KV1.3 over KV1.11.
The HsTX1[R14A] toxin has been shown to be highly resistant to proteolysis and stable in plasma1. This resistance, stabilized by four disulfide bridges, is superior to that of ShK analogues, including the clinical candidate ShK-186, which contains only three disulfide bridges3.
Pharmacokinetic studies indicate that both intravenous and subcutaneous applications are viable for the delivery of this potent peptide4. Additionally, HsTX1[R14A] has shown efficacy in a model of rheumatoid arthritis, suggesting its potential as a therapeutic agent for effector memory T cells (TEM) cell-mediated autoimmune diseases5. Its high stability and bioavailability make HsTX1[R14A] toxin an excellent candidate for further development as a therapeutic lead and as a probe for therapeutic applications6.
KV1.3 upregulation is implicated in various autoimmune and neuroinflammatory diseases, including rheumatoid arthritis, psoriasis, multiple sclerosis, and type I diabetes. While the therapeutic potential of KV1.3 blockade has been well-characterized in autoimmune diseases driven by effector memory T cells, emerging evidence suggests that KV1.3 also plays a role in diseases involving T helper cells, macrophages, microglia, and class-switched B cells3. This expanded understanding of KV1.3's role in various cell types and diseases further highlights the potential therapeutic value of HsTX1[R14A] and similar KV1.3 blockers.
