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Hemitoxin (HTX) is a new K+ channel blocker isolated from the venom of the Iranian scorpion Hemiscorpius lepturus. It represents only 0.1% of the venom proteins, and displaces [125I]α‐dendrotoxin from its site on rat brain synaptosomes with an IC50 value of 16 nm. The amino acid sequence of HTX shows that it is a 35‐mer basic peptide with eight cysteine residues, sharing 29–69% sequence identity with other K+ channel toxins, especially with those of the αKTX6 family. A homology‐based molecular model generated for HTX shows the characteristic α/β‐scaffold of scorpion toxins. The pairing of its disulfide bridges, deduced from MS of trypsin‐digested peptide, is similar to that of classical four disulfide bridged scorpion toxins (Cys1–Cys5, Cys2–Cys6, Cys3–Cys7 and Cys4–Cys8). Although it shows the highest sequence similarity with maurotoxin, HTX displays different affinities for Kv1 channel subtypes. It blocks rat Kv1.1, Kv1.2 and Kv1.3 channels expressed in Xenopus oocytes with IC50 values of 13, 16 and 2 nm, respectively. As previous studies have shown the critical role played by the β‐sheet in Kv1.3 blockers, we suggest that Arg231 is also important for Kv1.3 versus Kv1.2 HTX positive discrimination. This article gives information on the structure–function relationships of Kv1.2 and Kv1.3 inhibitors targeting developing peptidic inhibitors for the rational design of new toxins targeting given K+ channels with high selectivity.

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