HsTX1[R14A]

Overview

HsTX1[R14A] is a research-grade protein/peptide reagent used in research settings. It is commonly applied as a tool reagent related to KV1.3 biology and/or assay development. It is supplied in Lyophilized format to support flexible downstream use in RUO workflows. Researchers commonly pair it with applications such as Electrophysiology.

Key elements and design rationale

• Molecular identity: MW: 3733.4 Da, Formula: C146H239N51O46S9.
• Source / origin: Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black scorpion).
• Quality attributes: Purity: ≥98% (HPLC); Bioassay tested: Yes; Sterile / endotoxin-free: No.

Modifications

Disulfide bonds between: Cys3-Cys24, Cys9-Cys29, Cys13-Cys31 and Cys19-Cys34 Cys34 = C-terminal amidation

When used as a biochemical or pharmacological tool, results are best interpreted relative to the experimental system (species, expression level, and assay readout) and with appropriate negative and competition-style controls where relevant. This product is intended for research use only.

Biological background

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.

Research relevance and current trends

• Using high-specificity ligands, toxins, and engineered peptides to dissect closely related receptor/channel subtypes and signaling microdomains.
• Pairing labeled (e.g., fluorescent) proteins/peptides with advanced imaging to map surface expression, trafficking, and nanoscale organization.
• Increasing emphasis on reproducibility through standardized characterization (identity, purity, and lot QC) and transparent reporting of reagent attributes.

Common research applications

• Electrophysiology: commonly used to compare signal, binding, or functional readouts across conditions without implying a specific protocol.

Across these use cases, changes in signal or functional readout are generally interpreted as evidence of differences in target abundance, accessibility, or engagement, but alternative explanations (matrix effects, off-target interactions, or assay artifacts) should be considered.

Notes for experimental interpretation

• Assay context matters: binding assays, functional modulation, and detection workflows can yield different readouts even for the same target system.
• Target complexity: closely related family members, splice variants, and post-translational modifications can influence apparent specificity and potency.
• Matrix and sample effects: buffer composition, detergents, and biological matrices may alter stability or apparent activity; interpret with appropriate controls.
• Control concepts: include negative controls and orthogonal validation (e.g., genetic perturbation or alternative reagents) to support robust interpretation.

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