131-I-TM-601

Synonyms :
TM-601

Status : investigational

Description

131-I-TM-601 is investigated in clinical trials for treating brain cancer. 131-I-TM-601 is a solid. Tx binds to and reduces the activity of a matrix metalloproteinase (MMP) that regulates functioning of the chloride channels on cell membranes. TM-601 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 ((131)I-TM-601) as a means of targeting radiation to tumor cells in the treatment of brain cancer. The selective effects of TM-601 are regulated by its action on MMP2 receptors.

Used

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

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.

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.

Toxic Effect

Found safe in clinical trials.

Chemical Classification

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.

Stilbenes

Organic compounds

Phenylpropanoids and polyketides

Stilbenes

Chemical Name

TM-601

Calculated Property

kind Value Source
logP 5.85 ALOGPS
logS -6.7 ALOGPS
Water Solubility 6.91e-05 g/l ALOGPS
logP 6.52 ChemAxon
IUPAC Name {2-[4-(1,2-diphenylbutyl)phenoxy]ethyl}dimethylamine ChemAxon
Traditional IUPAC Name {2-[4-(1,2-diphenylbutyl)phenoxy]ethyl}dimethylamine ChemAxon
Molecular Weight 373.5304 ChemAxon
Monoisotopic Weight 373.240564619 ChemAxon
SMILES CCC(C(C1=CC=CC=C1)C1=CC=C(OCCN(C)C)C=C1)C1=CC=CC=C1 ChemAxon
Molecular Formula C26H31NO ChemAxon
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 ChemAxon
InChIKey InChIKey=YUFAHBUWIVNVNJ-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 12.47 ChemAxon
Refractivity 118.67 ChemAxon
Polarizability 44.5 ChemAxon
Rotatable Bond Count 9 ChemAxon
H Bond Acceptor Count 2 ChemAxon
H Bond Donor Count 0 ChemAxon
pKa (strongest basic) 8.78 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon