chlorotoxin

Chlorotoxin is a peptide toxin derived from the venom of the deathstalker scorpion (Leiurus quinquestriatus). It is a small, cysteine-rich peptide of about 36 amino acids, stabilized by multiple disulfide bonds. Chlorotoxin was first characterized in the 1990s.

Biochemical studies show that chlorotoxin binds with high affinity to several cell-surface targets that are enriched in malignant cells, notably chloride channels such as ClC-3 and the extracellular matrix–metalloproteinase MMP-2. Binding to these targets is associated with inhibition of tumor cell migration and invasion in vitro, particularly in glioma cell models; results have also been observed in some animal models.

Applications in research and medicine: The selective tumor binding has led to the development of chlorotoxin derivatives as diagnostic and therapeutic targeting agents. A synthetic derivative, TM-601, has been studied in clinical trials as a radiolabeled or conjugated imaging agent for malignant gliomas and other tumors.

Chlorotoxin is also used to deliver fluorescent dyes, nanoparticles, or radioconjugates to tumor tissue in preclinical models, enabling tumor imaging or targeted therapy. Development has emphasized imaging and targeted delivery rather than broad clinical use.

Current status: While chlorotoxin and its derivatives showed promise for tumor imaging and targeted delivery, they have not become approved treatments, and progress has faced challenges. Research continues to explore its utility as a tumor-targeting ligand and diagnostic tool.