Uses
Leucomethylene blue (TRx0237) mesylate, an orally active second-generation tau protein aggregation inhibitor (Ki of 0.12 μM), could be used for the study of Alzheimer's Disease. Leucomethylene blue mesylate is a common reduced form of Methylene Blue, Methylene Blue is a member of the thiazine class of dyes[1][2][3].
Biological Activity
TRx 0237 mesylate (LMTX, Hydromethylthionine) is a second-generation tau protein aggregation inhibitor. For the treatment of Alzheimer's disease and frontotemporal dementia.
in vitro
TRx 0237 (LMTX) is a second-generation tau aggregation inhibitor for the treatment of Alzheimer's disease and frontotemporal dementia. It is a purified form of methylene blue, an ancient drug widely used in Africa to treat malaria and methemoglobinemia. In vitro experiments demonstrated that 0.16 μM TRx 0237 interfered with double helical filaments (PHF) isolated from Alzheimer's disease patient brain tissue.
in vivo
TRX-0237 mesylate dose-dependently rescues learning impairment in L1 (a mouse strain overexpressing truncated tau protein) and restores its behavioral resilience in the water maze test (minimum dose administered: 9 mg MT/kg). In L66 (a mouse strain overexpressing full-length tau-P301S/G335D), it modulates its motor learning (effective dose: 4 mg MT/kg). It reduced the number of tau-active neurons, especially in the hippocampus and entorhinal cortex of L1, and more generally in the L66 strain.
target
| Target | Value |
| tau protein aggregation |
References
[1] Gaudette NF, et al. Determination of methylene blue and leucomethylene blue in male and female Fischer 344 rat urine andB6C3F1 mouse urine. J Anal Toxicol. 2005 Jan-Feb;29(1):28-33. DOI:
10.1093/jat/29.1.28[2] Zhenhua Liu, et al. Amyloid β and tau are involved in sleep disorder in Alzheimer's disease by orexin A and adenosine A(1) receptor. Int J Mol Med. 2019 Jan;43(1):435-442. DOI:
10.3892/ijmm.2018.3935[3] Francesco Panza, et al. Tau aggregation inhibitors: the future of Alzheimer's pharmacotherapy Expert Opin Pharmacother. 2016;17(4):457-61. DOI:
10.1517/14656566.2016.1146686
