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Chlorotoxin is a 36 amino-acid peptide from the venom of the Israeli scorpion Leiurus quinquestriatus with anticancer activity. Chlorotoxin is a chloride channel blocker.

Chlorotoxin (Chlorotoxin) preferentially binds to tumor cells and has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has potential as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Chlorotoxin is shown to bind glioma cells, but is unable to bind normal rat astrocytes and Te671, a human rhabdomyosarcoma cell line. Chlorotoxin inhibits the migration of U251MG (glioma) cells, with an IC50 of 600 nM[2]. Chlorotoxin binds to glioma cells is specific and involves high affinity (Kd=4.2 nM) and low affinity (Kd=660 nM) binding sites[3].Small conductance chloride channels are shown to be potently blocked by Chlorotoxin. Chlorotoxin has been used as a general pharmacological tool to investigate the function of chloride channels[4].

Chlorotoxin shows insecticidal activity on insects and other invertebrates. After the administration of I-Chlorotoxin to tumor-bearing mice, the peptides accumulated within the tumor[2].Chlorotoxin selectively accumulates in the brain of tumor-bearing mice with calculated brain: muscle ratios of 36.4% of injected dose/g (ID/g), as compared to 12.4%ID/g in control animals[3].

[1]. DeBin JA, et al. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol. 1993 Feb;264(2 Pt 1):C361-9. [2]. Ojeda PG, et al. Chlorotoxin: Structure, activity, and potential uses in cancer therapy. Biopolymers. 2016 Jan;106(1):25-36. [3]. Soroceanu L, et al. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998 Nov 1;58(21):4871-9. [4]. Dardevet L, et al. Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins (Basel). 2015 Mar 27;7(4):1079-101.

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