Chlorotoxin I-131 is a synthetic version of a neurotoxin investigated in clinical trials for treating brain cancer. Chlorotoxin was originally isolated from the venom of the Israeli scorpion Leiurus quinquestriatus, and has potential as a tumor imaging agent based on its selective binding to tumor cells. Molecular targets for Chlorotoxin include voltage-gated chloride channels (GCC), calcium-dependent phospholipid-binding protein Annexin-2, and the inducible extracellular enzyme Matrix Metalloproteinase-2 (MMP-2). Chlorotoxin reduced the migration ability of glioma cells through tight extracellular spaces in the brain tissue by inhibition of the MMP2 because this prevented the cells from shrinking and releasing from the extracellular matrix. Chlorotoxin is a small 36-amino-acid peptide that selectively binds to glioma cells but not normal brain parenchyma. The synthetic version of this peptide has been manufactured and covalently linked to iodine 131 as a means of targeting radiation to tumor cells in the treatment of brain cancer.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). | 2007-03 |
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| Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. | 2006-08-01 |
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| TransMolecular receives FDA approval for 131-I-TM-601 IND application. | 2002-04 |
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| Use of chlorotoxin for targeting of primary brain tumors. | 1998-11-01 |
| Substance Class |
Protein
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| Protein Type | PEPTIDE |
| Protein Sub Type | |
| Sequence Origin | INSECT |
| Sequence Type | COMPLETE |
| Record UNII |
544WOQ7W6W
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| Record Status |
Validated (UNII)
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FDA ORPHAN DRUG |
152201
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DB05462
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100000183818
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544WOQ7W6W
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admin on Mon Mar 31 18:00:08 GMT 2025 , Edited by admin on Mon Mar 31 18:00:08 GMT 2025
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| 1_2 | 1_19 |
| 1_5 | 1_28 |
| 1_16 | 1_33 |
| 1_20 | 1_35 |
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TARGET->RADIOLIGAND |
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ACTIVE MOIETY |
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Structural Modifications
| Modification Type | Location Site | Location Type | Residue Modified | Extent | Fragment Name | Fragment Approval |
|---|---|---|---|---|---|---|
| AMINO ACID SUBSTITUTION | [1_29] | TYROSINE | IOTYROSINE I-131 | Q1M94GA18P |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| MOL_WEIGHT:CALCULATED | CHEMICAL |
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| Molecular Formula | CHEMICAL |
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