TRX-0237 mesylate
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MedKoo CAT#: 526653

CAS#: 1236208-20-0 (mesylate)

Description: Hydromethylthionine, also known as LMTM and Leucomethylene Blue, is a apotent tau aggregation inhibitor for the treatment of Alzheimer's disease (AD) and frontotemporal dementia. Hydromethylthionine showed pharmacological activity on brain structure and function as both monotherapy and as an add-on to symptomatic treatment in certain patients with Alzheimer’s disease.

Chemical Structure

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TRX-0237 mesylate
CAS# 1236208-20-0 (mesylate)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526653
Name: TRX-0237 mesylate
CAS#: 1236208-20-0 (mesylate)
Chemical Formula: C18H27N3O6S3
Exact Mass: 0.00
Molecular Weight: 477.609
Elemental Analysis: C, 45.27; H, 5.70; N, 8.80; O, 20.10; S, 20.14

Price and Availability

Size Price Availability Quantity
10mg USD 110 Ready to ship
25mg USD 220 Ready to ship
50mg USD 380 Ready to ship
100mg USD 685 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
1g USD 3850 Ready to ship
2g USD 6450 Ready to ship
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Related CAS #: 613-11-6 (free base)   1236208-20-0 (mesylate)   61-73-4 (chloride)   951131-15-0 (HBr)  

Synonym: Hydromethylthionine mesylate; TRX-0237; TRX 0237; TRX0237; LMTX. L-MTx; LMT-X; Leuco-MTx; Methylene blue mesylate. Leuco-methylonium bis(hydromethanesulfonate)

IUPAC/Chemical Name: N3,N3,N7,N7-tetramethyl-10H-phenothiazine-3,7-diamine dimethanesulfonate

InChi Key: SPCMQFLNOVTUBM-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H19N3S.2CH4O3S/c1-18(2)11-5-7-13-15(9-11)20-16-10-12(19(3)4)6-8-14(16)17-13;2*1-5(2,3)4/h5-10,17H,1-4H3;2*1H3,(H,2,3,4)

SMILES Code: CN(C1=CC(SC2=CC(N(C)C)=CC=C2N3)=C3C=C1)C.OS(=O)(C)=O.OS(=O)(C)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: Related CAS# 613-11-6 (free base) 1236208-20-0 (mesylate); 61-73-4 (chloride)

Biological target: Leucomethylene blue (Mesylate) is a common reduced form of Methylene Blue which is a member of the thiazine class of dyes and is used as an antiseptic and therapeutic agent.
In vitro activity: The level of the 19-kDa h-α-Syn species relative to the non-specific 50-kDa immunoreactivity was reduced in differentiated DH60.21 neurons following treatment with LMTM (leuco-methylthioninium bis(hydro- methanesulfonate). A representative immunoblot is shown in Figure2A. The EC50 value (±SE) for LMTM was 1.11 ± 0.28 μM (n = 6). As shown in Figure2B, LMTM had either no or minimal effect on expression of h-α-Syn mRNA in undifferentiated and differentiated neurons, respectively. The state of h-α-Syn expressed in cells was partially characterized by differential centrifugation and detergent extraction using Triton X-100 in the presence or absence of LMTM treatment (Figure2C). Following treatment with LMTM in the absence of Triton X-100, the overall quantity of h-α-Syn was reduced by approximately 85% and this was found exclusively in the FP fraction following high-speed centrifugation. When LMTM treatment was combined with Triton X-100, almost all of the remaining h-α-Syn was transferred to the high-speed supernatant (FS) fraction. Quantitative densitometry showed that levels of the non-specific 50-kDa band were not affected by the addition of LMTM (data not shown). LMTM may therefore have potential as a disease-modifying treatment for synucleinopathies including PD and dementia with Lewy bodies. Front Mol Neurosci. 2017; 10: 447. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767730/
In vivo activity: The effect of either LMTM (leuco-methylthioninium bis (hydromethane-sulfonate) alone or chronic rivastigmine prior to LMTM treatment of tau transgenic mice expressing the short tau fragment that constitutes the tangle filaments of AD (Alzheimer’s Disease) was examined. In wild-type mice, there was a significant, 2-fold increase in basal ACh levels in the hippocampus following LMTM treatment and a 30% reduction when mice received LMTM after chronic treatment with rivastigmine Fig. (2A). There was also an increase in mean synaptophysin levels measured in the hippocampus, visual cortex, diagonal band and septum following LMTM treatment alone. In tau transgenic L1 mice, LMTM alone produced significant increases in ACh release in the hippocampus, in glutamate release from synaptosomal brain preparations (not shown here), in synaptophysin levels, in mitochondrial complex IV activity and in spatial cognition. LMTM given alone produced a significant enhancement of complex IV activity in brain mitochondria from tau transgenic L1 mice. Conversely, counts of ChAT-positive neurons were reduced in L1 mice, but these were only partially restored by treatment with LMTM Fig. (5B). Curr Alzheimer Res. 2020 Mar; 17(3): 285–296. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403648/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 102.5 214.61
H2O 54.0 113.06

Preparing Stock Solutions

The following data is based on the product molecular weight 477.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Schwab K, Frahm S, Horsley D, Rickard JE, Melis V, Goatman EA, Magbagbeolu M, Douglas M, Leith MG, Baddeley TC, Storey JMD, Riedel G, Wischik CM, Harrington CR, Theuring F. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy. Front Mol Neurosci. 2018 Jan 10;10:447. doi: 10.3389/fnmol.2017.00447. PMID: 29375308; PMCID: PMC5767730. 2. Riedel G, Klein J, Niewiadomska G, Kondak C, Schwab K, Lauer D, Magbagbeolu M, Steczkowska M, Zadrozny M, Wydrych M, Cranston A, Melis V, Santos RX, Theuring F, Harrington CR, Wischik CM. Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model. Curr Alzheimer Res. 2020;17(3):285-296. doi: 10.2174/1567205017666200224120926. PMID: 32091331; PMCID: PMC7403648. 3. Schwab K, Frahm S, Horsley D, Rickard JE, Melis V, Goatman EA, Magbagbeolu M, Douglas M, Leith MG, Baddeley TC, Storey JMD, Riedel G, Wischik CM, Harrington CR, Theuring F. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy. Front Mol Neurosci. 2018 Jan 10;10:447. doi: 10.3389/fnmol.2017.00447. PMID: 29375308; PMCID: PMC5767730.
In vitro protocol: 1. Schwab K, Frahm S, Horsley D, Rickard JE, Melis V, Goatman EA, Magbagbeolu M, Douglas M, Leith MG, Baddeley TC, Storey JMD, Riedel G, Wischik CM, Harrington CR, Theuring F. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy. Front Mol Neurosci. 2018 Jan 10;10:447. doi: 10.3389/fnmol.2017.00447. PMID: 29375308; PMCID: PMC5767730.
In vivo protocol: 1. Riedel G, Klein J, Niewiadomska G, Kondak C, Schwab K, Lauer D, Magbagbeolu M, Steczkowska M, Zadrozny M, Wydrych M, Cranston A, Melis V, Santos RX, Theuring F, Harrington CR, Wischik CM. Mechanisms of Anticholinesterase Interference with Tau Aggregation Inhibitor Activity in a Tau-Transgenic Mouse Model. Curr Alzheimer Res. 2020;17(3):285-296. doi: 10.2174/1567205017666200224120926. PMID: 32091331; PMCID: PMC7403648. 2. Schwab K, Frahm S, Horsley D, Rickard JE, Melis V, Goatman EA, Magbagbeolu M, Douglas M, Leith MG, Baddeley TC, Storey JMD, Riedel G, Wischik CM, Harrington CR, Theuring F. A Protein Aggregation Inhibitor, Leuco-Methylthioninium Bis(Hydromethanesulfonate), Decreases α-Synuclein Inclusions in a Transgenic Mouse Model of Synucleinopathy. Front Mol Neurosci. 2018 Jan 10;10:447. doi: 10.3389/fnmol.2017.00447. PMID: 29375308; PMCID: PMC5767730.

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1: Shiells H, Schelter BO, Bentham P, Baddeley TC, Rubino CM, Ganesan H, Hammel J, Vuksanovic V, Staff RT, Murray AD, Bracoud L, Wischik DJ, Riedel G, Gauthier S, Jia J, Moebius HJ, Hardlund J, Kipps CM, Kook K, Storey JMD, Harrington CR, Wischik CM. Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia. J Alzheimers Dis. 2020;75(2):501-519. doi: 10.3233/JAD-191173. PMID: 32280089; PMCID: PMC7306898.


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9: Wilcock GK, Gauthier S, Frisoni GB, Jia J, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Schelter BO, Wischik DJ, Davis CS, Staff RT, Vuksanovic V, Ahearn T, Bracoud L, Shamsi K, Marek K, Seibyl J, Riedel G, Storey JMD, Harrington CR, Wischik CM. Potential of Low Dose Leuco-Methylthioninium Bis(Hydromethanesulphonate) (LMTM) Monotherapy for Treatment of Mild Alzheimer's Disease: Cohort Analysis as Modified Primary Outcome in a Phase III Clinical Trial. J Alzheimers Dis. 2018;61(1):435-457. doi: 10.3233/JAD-170560. PMID: 29154277; PMCID: PMC5734125.


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