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Chlorotoxin

Also known as: CTX, ClTx, TM-601, Tozuleristide, BLZ-100, Tumor Paint

Chlorotoxin is a 36-amino acid peptide isolated from the venom of the deathstalker scorpion (Leiurus quinquestriatus) that selectively binds to glioma cells and other tumors of neuroectodermal origin. Originally characterized as a chloride channel blocker, chlorotoxin gained prominence when researchers discovered it preferentially targets brain tumors while sparing normal tissue. This tumor-homing property led to its development as a fluorescent tumor-painting agent (tozuleristide/BLZ-100) and a potential targeted drug delivery vehicle for cancer treatment.

3 cited references·5 researched benefits

Quick Answer

Chlorotoxin is a 36-amino acid scorpion venom peptide that selectively binds to glioma and other neuroectodermal tumor cells while largely sparing normal brain tissue. It targets matrix metalloproteinase-2 (MMP-2) and annexin A2 on tumor cell surfaces. In clinical development as the fluorescent conjugate tozuleristide (BLZ-100), it serves as a "tumor paint" to help neurosurgeons visualize and remove brain tumors more precisely during surgery. Phase 2 clinical trials are ongoing.

Key Facts

Mechanism
Chlorotoxin binds to a molecular complex on tumor cell surfaces involving matrix metalloproteinase-2 (MMP-2), chloride channel ClC-3, and annexin A2. MMP-2 is overexpressed on glioma cells and facilitates tumor invasion through extracellular matrix degradation. Chlorotoxin binding inhibits MMP-2 activity, reduces chloride channel conductance (shrinking tumor cell volume and impairing migration), and triggers internalization of the peptide-receptor complex. When conjugated to indocyanine green (ICG) as tozuleristide, the fluorescent signal enables real-time intraoperative visualization of tumor margins. Chlorotoxin also inhibits tumor cell invasion and migration in vitro through MMP-2 and integrin pathway modulation.
Research Status
phase 2
Half-Life
Not well characterized in humans; rapid tissue binding
Molecular Formula
C₁₆₆H₂₅₈N₄₆O₄₈S₈
Primary Use
Other
Table of Contents

Benefits

  • Highly selective tumor-cell binding — targets gliomas and neuroectodermal tumors while sparing normal brain tissuestrong
  • Fluorescent tumor paint (tozuleristide) enables real-time intraoperative visualization of tumor margins, improving surgical resectionmoderate
  • Inhibits glioma cell migration and invasion through MMP-2 blockade in preclinical modelsmoderate
  • Potential drug-delivery vehicle — chlorotoxin conjugates can target chemotherapy or radioisotopes specifically to tumorspreliminary
  • Crosses the blood-brain barrier to some extent, enabling systemic administration for CNS tumorspreliminary

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intravenous infusion (tozuleristide/BLZ-100)0.5–3.0 mgSingle dose, 1–24 hours before surgeryAdministered as a single preoperative dose to allow tumor uptake and fluorescent labeling before surgical resection. Optimal imaging window is 2–24 hours post-infusion. Dose is under optimization in Phase 2 trials.
Intracavitary (TM-601, research)0.01–0.04 mgPost-surgical single dose or weekly × 3Iodine-131-labeled chlorotoxin (131I-TM-601) delivered directly into tumor resection cavity. Investigated in Phase 1/2 trials for recurrent glioma.

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Mild infusion-related reactions during tozuleristide administration (transient flushing, warmth)common
  • Transient green skin discoloration from ICG fluorescent dye componentcommon
  • Headache and nausea post-administrationrare
  • Theoretical risk of allergic reaction to scorpion venom-derived peptide in sensitized individualsserious

Frequently Asked Questions

What is tumor paint and how does it work?
Tumor paint refers to tozuleristide (BLZ-100), a fluorescent conjugate of chlorotoxin linked to indocyanine green (ICG). When injected intravenously before brain surgery, chlorotoxin selectively binds to tumor cells and accumulates in the tumor tissue. Under near-infrared fluorescence imaging during surgery, the tumor glows brightly against normal brain tissue, allowing neurosurgeons to see tumor margins in real time. This can improve the extent of surgical resection while minimizing damage to healthy brain tissue — a critical balance in brain tumor surgery.
Is chlorotoxin safe given that it comes from scorpion venom?
Chlorotoxin is a single purified peptide, not whole scorpion venom. In clinical trials, both tozuleristide and 131I-TM-601 have shown favorable safety profiles at therapeutic doses. The peptide targets specific molecular features of tumor cells (MMP-2, ClC-3, annexin A2) and has minimal activity on normal tissues. The synthetic production process ensures purity and consistency. Phase 1 and 2 trials have reported mostly mild adverse events (transient skin discoloration, mild infusion reactions) with no dose-limiting toxicities at tested ranges.
Can chlorotoxin treat brain cancer or only help visualize it?
Currently, the most advanced clinical application is tumor visualization (tozuleristide). However, chlorotoxin is also being developed as a therapeutic agent through two approaches: (1) as a radioimmunotherapy agent (131I-TM-601), where iodine-131-labeled chlorotoxin delivers targeted radiation to tumor cells, studied in Phase 1/2 trials for recurrent glioma; and (2) as a drug delivery vehicle, where chlorotoxin is conjugated to nanoparticles or chemotherapy agents to target them specifically to tumors. Both therapeutic approaches remain investigational.
What types of cancer does chlorotoxin target?
Chlorotoxin was originally discovered to bind glioma cells, but subsequent research has shown it targets a broader range of tumors. It binds to MMP-2/annexin A2 complexes overexpressed on glioblastoma, medulloblastoma, neuroblastoma, melanoma, small cell lung cancer, and prostate cancer cells. The common thread is neuroectodermal origin or high MMP-2 expression. Tozuleristide is being studied primarily for CNS tumors (glioma, pediatric brain tumors) and is also being explored for other solid tumors where real-time surgical visualization could improve outcomes.

References

  1. 1
    Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin(1998)PubMed ↗
  2. 2
    Tozuleristide (BLZ-100) for fluorescence-guided tumor visualization in pediatric CNS tumors: Phase 1 trial results(2020)PubMed ↗
  3. 3
    Chlorotoxin: structure, function, and potential as a cancer-targeting peptide(2012)PubMed ↗

Latest Research

Last updated: 2026-02-19