ADWX 1

Product Name:ADWX 1

Purity:95%

Molar Mass:4071.86

Chemical Formula:C169H281N57O46S7

Storage:Store at -20 degrees Celsius

Sequence:VGINVKCKHSRQCLKPCKDAGMRFGKCTNGKCHCTPK

Target:KV1.3 channel blocker

Application:ADWX 1 is a potent and selective KV1.3 channel blocker. KV1.3 is a voltage-gated potassium channel primarily expressed in immune cells, particularly in T lymphocytes. Blocking KV1.3 channels can modulate immune cell activity, making ADWX 1 of particular interest for therapeutic applications in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and psoriasis. By inhibiting these channels, ADWX 1 helps reduce the proliferation of autoreactive T cells, offering a potential pathway for immune regulation and inflammation control.

Current Research:

ADWX-1 is a synthetic peptide analog of the scorpion toxin BmKTX, engineered to selectively and potently inhibit the voltage-gated potassium channel Kv1.3. This channel plays a crucial role in the activation and proliferation of effector memory T (TEM) cells, which are implicated in various autoimmune diseases.

Structural Modifications

To enhance specificity and affinity for Kv1.3, three amino acid residues in BmKTX were substituted: Glycine at position 11 was replaced with Arginine, Isoleucine at position 28 with Threonine, and Aspartic acid at position 33 with Histidine. These modifications resulted in ADWX-1, which exhibits an IC?? of 1.89 pM for Kv1.3, indicating a 100-fold increase in potency compared to the native toxin.

Selectivity Profile

ADWX-1 demonstrates high selectivity for Kv1.3 over related channels, with an IC?? of 0.65 nM for Kv1.1 and negligible activity against Kv1.2. This selectivity is advantageous for targeting Kv1.3 in therapeutic applications without significantly affecting other potassium channels.

Therapeutic Potential

In animal models of autoimmune diseases, such as experimental autoimmune encephalomyelitis (EAE), ADWX-1 has been shown to reduce clinical symptoms and decrease inflammatory cell infiltration. It achieves this by inhibiting Kv1.3 channel activity, leading to suppression of calcium signaling and NF-??B activation in TEM cells. Consequently, the production of pro-inflammatory cytokines like IL-2 and IFN-?? is reduced, mitigating autoimmune responses.

Research Applications

ADWX-1 serves as a valuable tool for studying Kv1.3 channel physiology and its role in immune cell function. Its high potency and selectivity make it suitable for exploring therapeutic strategies aimed at modulating immune responses in autoimmune disorders.

Conclusion

The development of ADWX-1 underscores the potential of rational peptide design in creating highly specific ion channel inhibitors. Its efficacy in preclinical models highlights its promise as a therapeutic candidate for T cell-mediated autoimmune diseases.

Reference:

Yin, S. J., Jiang, L., Yi, H., Han, S., Yang, D. W., Liu, M. L., ... & Li, W. X. (2008). Different residues in channel turret determining the selectivity of ADWX-1 inhibitor peptide between Kv1. 1 and Kv1. 3 channels. Journal of proteome research, 7(11), 4890-4897.