High Purity J147 Powder (1146963-51-0)

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High Purity J147 Powder (1146963-51-0) Overview J147 is an exciting new compound that is extremely potent, safe in animal studies and orally active. J147 is a potential AD(Alzheimer's disease) therapeutic due to its ability to provide immediate cognition benefits, and it also has the potential to halt and perhaps reverse disease progression in symptomatic animals as demonstrated in these studies.

Base Information Name

J147 1/5

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CAS

1146963-51-0

Purity

98%

Chemical name

2,2,2-Trifluoroacetic acid 1-(2,4-Dimethylphenyl)-2-[(3-methoxyphenyl)methylene]hy drazide

Synonyms

N-(2,4-Dimethylphenyl)-2,2,2-trifluoro-N’-[(E)-(3-methoxy phenyl)methylene]acetohydrazide

Molecular Formula

C18H17F3N2O2

Molecular Weight

350.341 g/mol

Melting Point

177-178°C

InChI Key

HYMZAYGFKNNHDN-SSDVNMTOSA-N

Form

Solid

Appearance

White of off-white powder

Half Life

1.5 hrs in plasma and 2.5 hrs in brain

Solubility

Soluble to 100 mM in DMSO and to 100 mM in ethano

Storage Condition

Store at +4°C

Application

Experimental drug with reported effects against both Alzheimer’s disease and ageing in mouse models of accelerated aging.

Testing Document

Available

J147 (1146963-51-0) General Description J147 was first developed in 2011, and researchers have carried out several studies that show it can reverse memory loss and slow or reverse Alzheimer’s in mice. But until this study, they didn’t know how it worked within cells.

J147 (1146963-51-0) History The experimental drug J147 is something of a modern elixir of life; it’s been shown to treat Alzheimer’s disease and reverse aging in mice and is almost ready for clinical trials in humans. Now, Salk scientists have solved the puzzle of what, exactly, J147 does. In a paper published January 7, 2018, in the journal Aging Cell, they report that the drug binds to a protein found in mitochondria, the energy-generating powerhouses of cells. In turn, they showed, it makes aging cells, mice and flies appear more youthful.

This really glues together everything we know about J147 in terms of the link between aging and Alzheimer’s,” says Dave Schubert, head of Salk’s Cellular 2/5

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Neurobiology Laboratory and the senior author on the new paper. “Finding the target of J147 was also absolutely critical in terms of moving forward with clinical trials.”

J147 (1146963-51-0) Mechanism Of Action Scientists were able to show that J147 works by manipulating ATP, a protein in the mitochondria and the body’s mobile source of energy. When J147 was present, neurons were protected from toxicities associated with aging. Additional experiments showed that J147 increases the levels of ATP and promotes healthier, more stable mitochondria.

“We know that age is the single greatest contributing factor to Alzheimer’s, so it is not surprising that we found a drug target that’s also been implicated in aging,” said Josh Goldberg, the paper’s first author.

Scientists have long targeted the protein beta-amyloid, which accumulates in the brains of Alzheimer’s patients, but since age is the single biggest risk factor for dementia, a drug that targets it could be the piece of the puzzle researchers have been looking for. J147 could potentially be successful in other neurodegenerative diseases, too, like Parkinson’s.

“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age associated.”

J147 (1146963-51-0) Application Drug development has, for a long time, focused on removing the protein beta-amyloid, which accumulates in the brains of Alzheimer’s patients, to little success, but given that aging is by far the greatest risk factor for dementia, a drug that targets an aging process itself might be the final piece of the puzzle that researchers have been looking for.

J147 may potentially be successful in treating other neurodegenerative diseases, such as Parkinson’s. “People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Schubert. “But it may be that by targeting aging, we can treat or slow down many pathological conditions that are old-age associated.”

In the USA, J147 has completed the required toxicology testing in animals required by the FDA, and it currently has an Investigational New Drug (IND) status. The 3/5

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Investigational New Drug program is how a pharmaceutical company gets permission to move an experimental drug across state lines (normally to clinical investigators) before a marketing application for the drug is approved.

J147 entered a phase 1 human clinical trial in February 2019. This Phase I clinical study is a randomized, double-blind, placebo-controlled, parallel-design study to thoroughly assess the safety profile and PK properties of J147 in healthy subjects.

The study will include single ascending dose (SAD) in healthy young and elderly subjects. The trial is being run by Abrexa Pharmaceuticals, Inc.

J147 (1146963-51-0) More research J147 is an experimental drug with reported effects against both Alzheimer’s disease and ageing in mouse models of accelerated aging.

The approach that lead to development of the J147 drug was to screen candidate molecules for anti-aging effects, instead of targeting the amyloid plaques. It is contrary to most other approaches to developing drugs against Alzheimer’s disease that target the plaque deposits in the brain.

The J147 drug is also reported to address other biological aging factors, such as preventing the leakage of blood from microvessels in mice brains.[5] The development of J147 follows the chemical pharmacological way, contrary to biological ways that exploit e.g. use of bacteriophages.

Enhanced neurogenic activity over J147 in human neural precursor cells has its derivative called CAD-31. CAD-31 is enhancing the use of free fatty acids for energy production by shifting of the metabolic profile of fatty acids toward the production of ketone bodies, a potent source of energy in the brain when glucose levels are low.

The target molecule is a protein called ATP synthase, which is found in the mitochondria.

J147 (1146963-51-0) Document Download COA

J147 (1146963-51-0) Reference 1. “Experimental drug targeting Alzheimer’s disease shows anti-aging effects”(Press release). Salk Institute. 12 November 2015. Retrieved November 13, 2015.

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2. Joshua Goldberg et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 2018 DOI: 10.1111/acel.12715

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