leucomethylthioninium   Click here for help

GtoPdb Ligand ID: 9274

Synonyms: leuco-methylthioninium | LMTM | LMTX | TRx-0237 | TRx0237
Compound class: Synthetic organic
Comment: Leucomethylthioninium complexed with bromide or methane sulfonate (LMTX) was designed as a methylthioninium chloride (MTC, or methylene blue) analogue with improved pharmacokinetic properties [1]. MTC and LMTX are tau aggregation inhibitors with potential in Alzheimer's disease (AD) and other tau-opathies. We believe this is the compound being investigated in Phase 3 clinical trials as TRx0237.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 1
Hydrogen bond donors 3
Rotatable bonds 2
Topological polar surface area 46.21
Molecular weight 287.15
XLogP 2.68
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C[NH+](c1ccc2c(c1)Sc1c(N2)ccc(c1)[NH+](C)C)C
Isomeric SMILES C[NH+](c1ccc2c(c1)Sc1c(N2)ccc(c1)[NH+](C)C)C
InChI InChI=1S/C16H19N3S/c1-18(2)11-5-7-13-15(9-11)20-16-10-12(19(3)4)6-8-14(16)17-13/h5-10,17H,1-4H3/p+2
InChI Key QTWZICCBKBYHDM-UHFFFAOYSA-P
No information available.
Summary of Clinical Use Click here for help
Click here to link to a list of Phase 3 TRx0237 trials in patients with AD registered with ClinicalTrials.gov. Results presented at the Alzheimer's Association International Conference in Toronto (July 2016) and reported on the NewScientist website, suggest encouraging results in the sub-cohort of patients with mild-moderate AD, but not taking other anti-AD drugs. This group of patients exhibited improved cognitive and functional outcomes as well as a slowing of brain atrophy. These are preliminary findings, as yet unpublished in a peer-reviewed article.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Most neurodegenerative diseases are characterised by deposition of aberrantly processed and aggregated proteins, e.g. extraneuronal deposition of amyloid β and microtubule-associated protein tau in Alzheimer's plaques and filaments respectively. Inhibition of the formation of tau filaments/tangles is one strategy being evaluated for potential clinical effect in tauopathies [2]. Leucomethylthioninium is one such tau aggregation inhibitor.