NAV

Chlorotoxin I-131

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
Chlorotoxin I-131
DrugBank Accession Number
DB05462
Background

Chlorotoxin I-131 is investigated in clinical trials for treating brain cancer. Chlorotoxin I-131 binds to and reduces the activity of a matrix metalloproteinase (MMP) that regulates functioning of the chloride channels on cell membranes. Chlorotoxin is a small 36-amino-acid peptide that selectively binds to glioma cells but not normal brain parenchyma. It is a synthetic version of a neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus quinquestriatus. 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. The selective effects of Chlorotoxin I-131 are regulated by its action on MMP2 receptors.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 373.5304
Monoisotopic: 373.240564619
Chemical Formula
C26H31NO
Synonyms
  • I(131)-TM-601 (chlorotoxin)
External IDs
  • I(131)-TM-601
  • TM-601 I-131
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Pharmacology

Indication

Investigated for use/treatment in various forms of brain cancer; Malignant Glioma, Glioblastoma Multiforme, GBM, Anaplastic Astrocytoma, Oligo-Astrocytoma, Gliosarcoma

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Contraindications & Blackbox Warnings
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Pharmacodynamics

As a synthetic version of a neurotoxin isolated from the venom of the Giant Yellow Israeli scorpion Leiurus Quinquestriatus, TM-601 is a small 36 amino acid peptide that has been manufactured and covalently linked to iodine 131 ((131)I-TM-601). Its unique binding to gliomal cells makes it a unique means of targeting radiation to tumor cells in the treatment of brain cancer.

Mechanism of action

TX binds to and reduces the activity of a matrix metalloproteinase (MMP) that is regulates functioning of the chloride channels on cell membranes. CTX 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.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Found safe in clinical trials.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Diphenylmethanes / Phenylpropanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Alkyl aryl ether / Amine / Aromatic homomonocyclic compound / Benzenoid / Diphenylmethane / Ether / Hydrocarbon derivative / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
544WOQ7W6W
CAS number
Not Available
InChI Key
YUFAHBUWIVNVNJ-UHFFFAOYSA-N
InChI
InChI=1S/C26H31NO/c1-4-25(21-11-7-5-8-12-21)26(22-13-9-6-10-14-22)23-15-17-24(18-16-23)28-20-19-27(2)3/h5-18,25-26H,4,19-20H2,1-3H3
IUPAC Name
{2-[4-(1,2-diphenylbutyl)phenoxy]ethyl}dimethylamine
SMILES
CCC(C(C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1

References

General References
  1. Mamelak AN, Jacoby DB: Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 2007 Mar;4(2):175-86. [Article]
  2. Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA: Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50. [Article]
  3. Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H: Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998 Nov 1;58(21):4871-9. [Article]
  4. Authors unspecified: TransMolecular receives FDA approval for 131-I-TM-601 IND application. Expert Rev Anticancer Ther. 2002 Apr;2(2):139. [Article]
PubChem Compound
4369566
PubChem Substance
175427012
ChemSpider
3572093

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.91e-05 mg/mLALOGPS
logP5.85ALOGPS
logP6.52Chemaxon
logS-6.7ALOGPS
pKa (Strongest Basic)8.78Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area12.47 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity118.67 m3·mol-1Chemaxon
Polarizability44.5 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9955
Blood Brain Barrier+0.8495
Caco-2 permeable+0.884
P-glycoprotein substrateSubstrate0.6851
P-glycoprotein inhibitor IInhibitor0.5267
P-glycoprotein inhibitor IINon-inhibitor0.8262
Renal organic cation transporterInhibitor0.6724
CYP450 2C9 substrateNon-substrate0.7787
CYP450 2D6 substrateSubstrate0.8889
CYP450 3A4 substrateSubstrate0.6919
CYP450 1A2 substrateInhibitor0.9082
CYP450 2C9 inhibitorNon-inhibitor0.8418
CYP450 2D6 inhibitorInhibitor0.9214
CYP450 2C19 inhibitorNon-inhibitor0.8823
CYP450 3A4 inhibitorNon-inhibitor0.9393
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6783
Ames testNon AMES toxic0.8804
CarcinogenicityNon-carcinogens0.5742
BiodegradationNot ready biodegradable0.9741
Rat acute toxicity2.1637 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5748
hERG inhibition (predictor II)Inhibitor0.6865
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00xu-9736000000-a9b1edd6b1e6e42283be
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00xu-9713000000-7803ffb2bba602eac1f4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fk9-0129000000-0f00b15543e0abfaacfc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-9300000000-6b51e3cbd1046976f3e1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fk9-1669000000-66b14675e54af3f2fd53
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-1291000000-752eef4a87107ccd2a95
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-190.40257
predicted
DeepCCS 1.0 (2019)
[M+H]+192.96303
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.38853
predicted
DeepCCS 1.0 (2019)

Drug created at November 18, 2007 18:25 / Updated at July 18, 2023 22:56