Chlorotoxin-binding receptor complex (CLTX-R)

The Chlorotoxin-binding receptor complex is a specialized molecular assembly found predominantly on the surface of glioblastoma multiforme (GBM) cells and other neuroectodermal tumors (Deshane et al., 2003). This complex is primarily composed of Matrix Metalloproteinase-2 (MMP-2), Annexin A2, and the voltage-gated chloride channel ClC-3 (Tostes et al., 2017). Chlorotoxin, a peptide derived from scorpion venom, exhibits high affinity and specificity for this complex, which is minimally expressed in normal brain tissue (Soroceanu et al., 1998). Upon binding, the complex is internalized, leading to the downregulation of surface MMP-2 and inhibition of chloride ion flux, which collectively impairs the migratory and invasive capabilities of tumor cells (Veiseh et al., 2007). This unique binding profile has made the complex a primary target for intraoperative imaging agents like Tozuleristide (BLZ-100) and targeted therapies including radiopharmaceuticals and CAR T-cell treatments (Wang et al., 2020).

Other names

Chlorotoxin receptorCLTX receptorMMP-2/Annexin A2/ClC-3 complexGlioma-specific chlorotoxin binding site

Chlorotoxin binds to the receptor complex, triggering its rapid internalization and inhibiting the activity of MMP-2 and chloride channels, which reduces the invasive potential and motility of glioma cells (Veiseh et al., 2007; Deshane et al., 2003).