HsTX1[R14A]

Overview

Cat #: STH-310

Alternative Name Potassium channel toxin alpha-KTx 6.3 analogue

Lyophilized Powder yes

Origin Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black scorpion)

Source Synthetic peptide

MW: 3733.4 Da

Purity: ≥98% (HPLC)

Form Lyophilized from double distilled water (ddH₂O). May contain TFA as a residual counter ion.

Effective concentration 0.05 – 0.5 nM

Sequence ASCRTPKDCADPCAKETGCPYGKCMNRKCKCNRC -NH₂

Modifications Disulfide bonds between: Cys³-Cys²⁴, Cys⁹-Cys²⁹, Cys¹³-Cys³¹and Cys¹⁹-Cys³⁴Cys³⁴= C-terminal amidation

Structure

Molecular formula C₁₄₆H₂₃₉N₅₁O₄₆S₉

Activity HsTX1[R14A] is a potent and selective blocker of K_v1.3 voltage-gated K⁺ channels¹.

References-Activity

Rashid M.H. et al. (2014) Sci Rep., 4, 4509.

Accession number P59867

Shipping and storage The product is shipped as a lyophilized powder at room temperature. Upon receipt, store the product at -20°C. Protect from moisture.

Solubility Centrifuge the vial before adding solvent (10,000 x g for 5 minutes) to spin down all the powder to the bottom of the vial. The lyophilized product may be difficult to visualize. Add solvent directly to the centrifuged vial. Tap the vial to aid in dissolving the lyophilized product. Tilt and gently roll the liquid over the walls of the vial. Avoid vigorous vortexing. Light vortexing for up to 3 seconds is acceptable if needed.

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.

Storage of solutions The reconstituted solution can be stored at 4°C for up to 1 week. For longer periods (up to 6 months), small aliquots should be stored at -20°C. We do not recommend storing the product in working solutions for longer than a few days. Avoid multiple freeze-thaw cycles.

Our bioassay

Alomone Labs HsTX1[R14A] toxin inhibits K_V1.3 channels heterologously expressed in Xenopus oocytes.
A. Representative time course of HsTX1[R14A] (#STH-310) inhibition of normalized K_V1.3 current. Membrane potential was held at -80 mV, current was elicited by a 100 ms voltage ramp to +60 mV every 10 sec, and significantly inhibited by 0.5 nM (green) HsTX1[R14A] toxin.
B. Superimposed traces of K_V1.3 channel currents in the absence (control) and presence of 0.5 nM (green) HsTX1[R14A] toxin (taken from the recording in A).

References - Scientific background

Rashid, M.H. et al. (2014) Sci. Rep., 4, 4509.
Lebrun, B. et al. (1997) Biochem. J. 328, 321.
Tajti, G. et al. (2020), Biochem. Pharmacol., 181, 114146.
Bergmann, R. et al. (2017) Sci. Rep., 7, 3756.
Tanner M.R. et al. (2017) Clin. Immunol., 180, 45.
Wai D.C.C. et al. (2022) Bioconj. Chem., 33, 2197.

Scientific background

HsTX1[R14A] is an analogue of HsTX1, a 34-residue peptide toxin originally derived from the venom of the scorpion Heterometrus spinifer^1,2. In this analogue, arginine at position 14 is substituted with alanine, resulting in a potent and selective blocker of voltage-gated potassium channels (K_V1.3), with an IC50 of 45 ± 3 pM. HsTX1[R14A] exhibits more than 2,000-fold selectivity for K_V1.3 over K_V1.1¹.

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 (T_EM) 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.

K_V1.3 upregulation is implicated in various autoimmune and neuroinflammatory diseases, including rheumatoid arthritis, psoriasis, multiple sclerosis, and type I diabetes. While the therapeutic potential of K_V1.3 blockade has been well-characterized in autoimmune diseases driven by effector memory T cells, emerging evidence suggests that K_V1.3 also plays a role in diseases involving T helper cells, macrophages, microglia, and class-switched B cells³. This expanded understanding of K_V1.3's role in various cell types and diseases further highlights the potential therapeutic value of HsTX1[R14A] and similar K_V1.3 blockers.

Target K_V1.3

Lyophilized Powder

HsTX1[R14A] (#STH-310) is a highly pure, synthetic, and biologically active toxin.

Certificate of Analysis SDS

For research purposes only, not for human use

Last Update: 11/03/2025

Order Summary

HsTX1[R14A]

Overview

Applications

Citations

Specifications

Scientific Background

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