ShK-186

ShK-186, also known as Dalazatide, is a synthetic peptide derived from a naturally occurring toxin found in the venom of the sea anemone Stichodactyla helianthus. It is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, which is predominantly expressed in effector memory T cells. ShK-186 has been investigated for its potential therapeutic applications in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis.

Mechanism of Action

ShK-186 functions by selectively inhibiting the Kv1.3 potassium channel. This channel plays a crucial role in the activation and proliferation of effector memory T cells, which are implicated in the pathogenesis of various autoimmune diseases. By blocking Kv1.3, ShK-186 reduces the activity of these T cells, thereby modulating the immune response and potentially alleviating symptoms of autoimmune disorders.

Pharmacokinetics

The pharmacokinetic profile of ShK-186 has been studied in preclinical models. It is administered subcutaneously and has demonstrated a favorable safety profile. The peptide is designed to have a prolonged half-life, allowing for less frequent dosing in clinical settings.

Clinical Development

ShK-186 has undergone several phases of clinical trials. Early studies have shown promise in reducing disease activity in patients with autoimmune conditions. The drug is currently in development by Kineta, Inc., and has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of multiple sclerosis.

Potential Applications

The selective inhibition of Kv1.3 by ShK-186 makes it a promising candidate for the treatment of a variety of autoimmune diseases. Its ability to specifically target effector memory T cells without broadly suppressing the immune system could offer a therapeutic advantage over existing treatments.

Safety and Efficacy

In clinical trials, ShK-186 has been well-tolerated with a manageable safety profile. The most common adverse effects reported include mild injection site reactions. Efficacy data from early-phase trials suggest that ShK-186 can effectively reduce disease activity in conditions like psoriasis and rheumatoid arthritis.

Research and Future Directions

Ongoing research is focused on further elucidating the long-term safety and efficacy of ShK-186 in larger patient populations. Additionally, studies are exploring its potential use in other autoimmune and inflammatory diseases.

Also see

• Kv1.3 potassium channel
• Autoimmune disease
• Multiple sclerosis
• Rheumatoid arthritis
• Psoriasis

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