Modifications Disulfide bonds location- Cys3-Cys35, Cys12-Cys28 and Cys17-Cys32
Molecular formula C174H285N55O48S6
Activity ShK-235 is a potent blocker of Kv1.3 voltage-gated K+ channels that exhibits a 2250-fold selectivity for Kv1.3 over Kv1.1 channels1.
Shipping and storage The product is shipped as a lyophilized powder at room temperature. Upon receipt, store the products at -20°C. Protect from moisture.
Solubility Soluble in water. Centrifuge all product preparations before use (10000 x g, 5 min). For long-term storage in solution, we highly recommend preparing a stock solution in pure water (e.g., double-distilled water (ddH2O) at a concentration between 100-1000x of the final working concentration. Divide the solution into small aliquots and store at -20°C. Upon use, thaw the relevant vial and dilute in your working buffer. The preparation of fresh solutions in working buffers before use is recommended. Avoid multiple freeze-thaw cycles to maintain biological activity. Centrifuge all product preparations before use (10000 x g, 5 min).
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 ShK-235 blocks KV1.3 channels expressed in Xenopus oocytes.
A. Representative time course of ShK-235 (#STS-380) inhibition of normalized KV1.3 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 0.1 nM (green) ShK-235. B. Superimposed traces of KV1.3channelcurrents in the absence (control) and presence of 0.1 nM (green) ShK-235 (taken from the recording in A).
Scientific background
ShK-235 is a synthetic analog of ShK (Stichodactyla Toxin) (#STS-400), a native 35 amino acid peptidyl toxin originally isolated from the nematocyst of the sea anemone Stichodactyla helianthus1. Native ShK blocks the voltage-gated potassium (KV)1.3, KV1.1, KV1.4, and KV1.6 at subnanomolar concentrations2. Its synthetic analog, ShK-235, is a highly specific KV1.3 blocker with picomolar affinity and exhibited greater than 2250-fold selectivity for KV1.3 over KV1.1 and with very little block of other important KV subtypes (KV1.4 and KV1.6)3.
Kv channels play key roles in human physiology and pathology. The Kv1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases4. This channel maintains the membrane potential of a sub-set of T lymphocytes known as effector memory (TEM) T cells, that mediate and play a major role in the pathogenesis of autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes mellitus, rheumatoid arthritis (RA), and psoriasis5,6.