ImKTx88

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ImKTx88 is a small peptide toxin from the venom of the lesser brown scorpion, Isometrus maculatus. It selectively blocks potassium channels in the Kv1 family and belongs to the α-KTx subfamily. The name reflects the scorpion source, the Kv channel targets, and its clone number (88).

The mature toxin consists of 38 amino acids (about 4.3 kDa), derived from a 60-amino-acid precursor. It forms three disulfide bridges and adopts a structure with one N-terminal α-helix and three C-terminal anti-parallel β-sheets. This folding pattern, including a lysine-containing motif typical of α-KTx toxins, supports its role as a pore blocker.

ImKTx88 binds to the pore of Kv1.1, Kv1.2, and Kv1.3 channels, with the strongest affinity for Kv1.3 (IC50 ≈ 91 pM), and much weaker affinity for Kv1.1 (≈ 389 nM) and Kv1.2 (≈ 8.47 μM). Its action as a pore-blocking toxin makes Kv1.3 the primary target.

Kv1.3 channels are found in dendritic cells, lymphocytes, mitral cells, and in the nuclei of some cancer and brain cells. By blocking Kv1.3, ImKTx88 may disrupt membrane repolarization and calcium signaling, influencing cellular behavior.

Isometrus maculatus is considered mildly venomous; its sting can cause numbness and tingling. In research, ImKTx88 has reduced disease severity in a rat model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) by limiting harmful entry into the central nervous system and stabilizing the blood-brain barrier. It also helped preserve tight junction proteins and lowered inflammation-related molecules in the brain. These findings place ImKTx88 among candidates for MS treatment. In macrophages, reducing Kv1.3 activity lowered cell growth and migration, a pattern linked to cancer development.