chlorotoxin

Chlorotoxin is a 36-amino acid disulfide-rich peptide originally isolated from the venom of the deathstalker scorpion (Leiurus quinquestriatus). It acts as a neurotoxin and was first used to characterize chloride channels. Chlorotoxin selectively binds to glioma and other tumor cells, but not normal brain tissue, making it useful for targeting cancer cells in diagnosis, imaging, and therapy. Its mechanism involves blocking small-conductance chloride channels and binding preferentially to matrix metalloproteinase-2 (MMP-2), which is upregulated in gliomas and related cancers. This interaction inhibits MMP2 activity, reducing tumor cell migration by preventing cell shrinkage and detachment from the extracellular matrix. Chlorotoxin has been developed into synthetic analogs such as Iodine-131-labeled versions for targeted radiotherapy of brain tumors like glioma. It is under investigation for use against several solid tumors including melanoma, small cell lung carcinoma, neuroblastoma, and medulloblastoma[1][2][4][5][6][7][8]. Chlorotoxin’s ability to cross or deeply penetrate into brain tumors makes it promising for drug delivery applications in neuro-oncology. The exact primary receptor remains debated; besides MMP2 and chloride channels, annexin A2 has also been proposed as a possible target[1][6][8]. No major toxicities or immunogenic responses have been reported in human studies so far.

Other names

chlorotoxin