Alzheimer's drug J147: A Potent Curcumin Derivative J147 neurotrophic compound

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Alzheimer's drug J147: A Potent Curcumin Derivative J
147 Neurotrophic Compound
Content
1. What Is J147? ................................................................................................................................ 1
2. What Is J147 Made From? ............................................................................................................. 3
3. How Does J147 Work? .................................................................................................................. 5
4. J147 Rearch ................................................................................................................................... 5
5. J147 benefits ................................................................................................................................. 8
-Prevents Alzheimer's Disease .................................................................................................. 9
-Grows The Brain ..................................................................................................................... 10
-Improves Mitochondrial Function And Longevity .................................................................. 11
-Improves Memory .................................................................................................................. 12
-Protects Neurons ................................................................................................................... 12
-May Improve Anxiety ............................................................................................................. 13
6. J147 price .................................................................................................................................... 14
7. Where to get J147 ....................................................................................................................... 14
1. What Is J147?
Alzheimer's drug J147(1146963-51-0), is a potent neuroprotective and
neurotrophic compound. J147 protects against neurotoxicity in cortical
neurons in vitro (EC50 = 25 - 200 nM). J147. J147 reverses cognitive
impairment in aged Alzheimer's disease mice. J147 is an exciting new
compound that is extremely potent, safe in animal studies and orally active.
J147 is a potential AD therapeutic due to its ability to provide immediate
cognition benefits, and it also has the potential to halt and perhaps reverse
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disease progression in symptomatic animals as demonstrated in these
studies.
J147 Technical Data
Name
J147,J-147
CAS 1146963-51-0
Synonyms
N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N-[(E)-(3-methoxyphenyl)methylideneamino]aceta
mide; J-147; 1146963-51-0; N-(2,4-Dimethylphenyl)-2,2,2-trifluoro-N'-(3-methoxybenzyli
dene)acetohydrazide; CHEMBL2387144; SCHEMBL12995834; 3752AH; AKOS024458485;
CS-3688; AK279964; BC600735; HY-13779; 2,2,2-Trifluoroacetic acid 1-(2,4-dimethylp
henyl)-2-[(3-methoxyphenyl) methylene]hydrazide; J 147|2,2,2-Trifluoroacetic acid 1-(2,
4-Dimethylphenyl)-2-[(3-methoxyphenyl)methylene]hydrazide
J147, A potent neuroprotective and neurotrophic compound,under the IUPAC name
N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N-[(E)-(3-methoxyphenyl)methylideneamino]aceta
Descriptio mide, a phenyl hydrazide compound that has been shown to prevent memory defici
n
ts in an Alzheimer’s disease mouse model. in vitro: A potent neuroprotective and n
eurotrophic compound (EC50 = 25 - 200 nM) in vivo: Reduces soluble Aβ40 and A
β42 levels and increases BDNF levels in the hippocampus
Application Implicated in Alzheimer's disease
Molecular
Formula
C18H17F3N2O2
Molecular
Weight
350.3349896
Melt Point 177-178°C
Appearanc
White or off-white, light yellow powder
e
Solubility
Soluble to 100 mM in DMSO and to 100 mM in ethanol
Storage Store in a cool and dry place and at 0 - 4℃ for short term (days to weeks) or -3
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7℃ for long term (months to years).
Brief
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Purity >=99.8%
MSDS
Package
Inquire
Customization
2. What Is J147 Made From?
J147 is an exciting new compound that is extremely potent, safe in animal
studies and orally active. J147 is a potential AD 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. Unlike the
current drugs approved for Alzheimer's Disease, J147 is neither an
acetylcholinesterase inhibitor nor a phosphodiesterase inhibitor, yet it
enhances cognition with a short-term treatment. So, what is j147 made
from?
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According to salk institute j147 study, J147 is a curcumin derivative(j147
curcumin),J147 is a modified version of a molecule (curcumin) found in the
curry spice turmeric. Curcumin is a curry spice with multiple biological
activities that is also effective in transgenic AD mouse models. To improve
the potency and pharmacokinetic properties of curcumin, the authors
synthesized a series of hybrid molecules between curcumin and
cyclohexyl-bisphenol A (CBA), a compound that has neurotrophic activity
which curcumin lacks. The best compound from this initial synthesis was
CNB-001, a molecule that has improved stability over curcumin(j147
curcumin)and that is neuroprotective in multiple neurotoxicity assays in
which curcumin is inactive. Next, the authors generated a large number of
derivatives of CNB-001 and selected the best compound on the basis of
activity in our multiple toxicity assays. The result was a much more potent
molecule called J147. Further experimentation found that J147 was broadly
neuroprotective compound with memory enhancing activity in aged rodents
as well as AD transgenic mice. The neurotrophic and memory-enhancing
activities of J147 were found to be associated with an increase in brain
derived neurotrophic factor (BDNF) levels and the expression of BDNF
responsive proteins, enhancement of LTP, synaptic protein preservation, the
reduction of markers for oxidative stress and inflammation, the reduction of
amyloid plaques, and lower levels of soluble Aβ1–42 and Aβ1–40. Therefore,
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the range of biological activities of J147 relevant to human AD is also much
more extensive than any of the compounds that have failed in clinical trials.
In addition, J147 is very potent, has good medicinal chemical properties for a
CNS drug, is apparently safe, and is orally active. Thus, J147 is an exciting
new compound with the potential to be an AD therapeutic by slowing
disease progression through neuroprotection as well as providing immediate
cognition benefits.
3. How Does J147 Work?
Alzheimer's drug 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 dose
J147 work within cells. They 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.
4. J147 Rearch
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In a paper published on January 7, 2018 in the journal Aging Cell, researchers
from Salk Institute J147 for Biological Studies reported previously unknown
details about how the drug, made from a
version of a molecule found in curcumin,
modified
works in
the brain. They found it binds to a protein in
mitochondria, the cells responsible for
generating energy. In doing so, it makes cells
appear
younger—at least in the mice the drug has been tested on so far.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 J147 clinical trials
in humans(j147 human trials).
We know that Alzheimer’s disease is linked to ageing, in that the elderly are
most susceptible to experiencing the disorder, but just how deep are the ties?
A new study by researchers in the US explains more about the relationship
between ageing and Alzheimer’s, with continued testing of an experimental
drug candidate called J147 revealing unforeseen benefits in the latest
research. In testing on rodents, the drug surprised researchers by showing
unexpected anti-ageing effects on mice.
In the new work, led by Schubert and Salk Research Associate Josh Goldberg,
the team used several approaches to home in on what J147 is doing. They
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identified the molecular target of J147 as a mitochondrial protein called ATP
synthase that helps generate ATP—the cell’s energy currency—within
mitochondria. They showed that by manipulating its activity, they could
protect neuronal cells from multiple toxicities associated with the aging brain.
Moreover, ATP synthase has already been shown to control aging in C.
elegans worms and flies.
When the animals were treated with J147 they showed better memory and
cognition, healthier blood vessels in the brain, and other improved
physiological features.
“Initially, the impetus was to test this drug in a novel animal model that was
more similar to 99 percent of Alzheimer’s cases,” said Antonio Currais, a
researcher in the Cellular Neurobiology Laboratory at the Salk Institute for
Biological Studies in California. “We did not predict we’d see this sort of
anti-ageing effect, but J147 made old mice look like they were young, based
upon a number of physiological parameters.”
J147 takes a different approach to many other drugs developed to combat
Alzheimer’s disease. “While most drugs developed in the past 20 years target
the amyloid plaque deposits in the brain (which are a hallmark of the disease),
none have proven effective in the clinic,” said David Schubert, senior author
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of the study. Instead, the treatment focuses on what the researchers say is the
most obvious major risk factor for the disease: old age.
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.”
The team is already performing additional studies on the molecules that are
altered by J147’s effect on the mitochondrial ATP synthase—which could
themselves be new drug targets. J147 has completed the FDA-required
toxicology testing in animals, and funds are being sought to initiate phase 1
J147 clinical trials in humans((j147 human trials).
5. J147 benefits
J147 is an exciting new compound that is extremely potent, safe in animal
studies and orally active. J147 is a potential AD therapeutic due to its ability
to provide immediate cognition benefits, and it also has the potential to halt
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and perhaps reverse disease progression in symptomatic animals. J147
benefits may include:
-Prevents Alzheimer's Disease
J147 reverses cognitive impairment in a mouse model of Alzheimer’s Disease
(AD).
J147 can improve Amyloid-Beta (Aβ) metabolism and reduce levels in the
brain by reducing protein levels of β-Secretase (BACE).
In animal models of AD, J147 can protect BBB permeability homeostasis and
improve vascular function in the brain.
J147 can also significantly increase levels of Docosahexaenoic Acid (DHA) in
the brain.
It can also restore Glutamate levels (synthesized from the TCA intermediate
α-ketoglutarate) in the brain.
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-Grows The Brain
J147 can improve synaptic plasticity in the brain and induce its growth.
J147 improves synaptic plasticity by maintaining the expression of
Synaptophysin (a synaptic vesicle protein that is reduced in both aging and
AD and is considered a biomarker for synapse loss).
J147 grows the brain by increasing levels of both Nerve Growth Factor (NGF)
and Brain-Derived Neurotrophic Factor (BDNF).
A synthetic derivative of J147, T-006 (more discussed below on how to make
it), can also improve neurite outgrowth by regulating the PI3K/AKT pathway
and increasing NGF levels.
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-Improves Mitochondrial Function And Longevity
J147 is very effective in preventing oxidative stress and improving
mitochondrial function.
For example, J147 increases mitochondrial function by improving ATP levels
(inhibiting ATP synthase, specifically ATP5A).
By inhibiting ATP synthase, J147 can reduce toxic metabolites that cause
excitotoxicity.
This allows for more healthy/younger mitochondria (on a molecular level by
modulating the AMPK/mTOR pathway).
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For example, fruit flies that were given J147 had a longer lifespan (9.5-12.8%)
due to the effects on mitochondria.
J147 can also reduce aging of the brain from use of γ-glutamyl amino acids
and BCAAs.
-Improves Memory
It enhances memory in both AD mice and normal aged animal models.
Even in very old animal models, J147 can reverse severe cognitive deficits.
J147 can also improve spatial memory and enhance Long-Term Potentiation
(LTP).
-Protects Neurons
J147 does not specifically need BDNF to be neuroprotective.
J147 also rescues neurons Glutathione (GSH) depletion.
J147 is also neuroprotective against glucose starvation.
In AD brain's, Heme Oxygenase 1 (HO-1) as a pro-oxidant, instead of an
antioxidant, while 5-Lipoxygenase (5-LOX) recruits other immune cells to
induce an inflammatory response.
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J147 is able to reduce HO-1 levels and inhibit 5-LOX.
T-006 at very low concentrations can rescue neurons from death (prevents
reactive oxidative/nitrogen species stress in brain and glutamate-induced
excitotoxicity).
T-006 also inhibits NMDA overactivation, making it 100 times more potent
than Memantine.
-May Improve Anxiety
J147 may have some potential in improving Anxiety levels.
In animal models with AD, J147 was able to improve anxiety levels during
maze tests.
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6. J147 price
J147 can be bought online(J147 buy) from certain vendors, if you do want to
spend $$$ on J147, it goes for around 10 mg / $165.
7. Where to get J147
Aasraw Biochemical Technology Company Limited has recently started the
manufacturing of the much-anticipated J147(1146963-51-0) powder. While it
was first developed in 2011, the company started commercial production of
the powder only recently. Aasraw Biochemical Technology Company Limited
can actually produce the chemical intermediaries and active pharmaceutical
ingredients in clinical trials. Hence, distributors can now demand for smaller
quantities of the powder or as needed, and with good J147 price of course.
According to the researchers, J147(1146963-51-0) powder does not evidently
metabolize the hydrazine or aromatic amines. “Basically, the powder is
derived from the regularly used component of curry spices called ‘curcumin’,
which is known for low toxicity. The protein is ATP synthase. Our researchers
clearly showed that if ATP synthase activity got reduced, the neuronal cells
would be protected from several toxicities associated with brain ageing,” said
one of the senior researchers associated with Aasraw Biochemical
Technology Company Limited.
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The CEO and managing director of Aasraw Biochemical Technology said, “We
look toward offering pharmaceutical products high on quality and less in
pricing. Our researchers strive to invent safe and effective raw powders and
we have to admit that without the assistance from several studios, colleges
and enterprises, we wouldn’t have managed to improve the manufacturing
technology.
So, if you try to get J147(J147 buy) online, AASraw is a not bad choice. They
can provide all the technical documents of J147, COA,
HPLC,HNMR,MSDS...etc. Fully stated that AASraw is professional, and
the only source of J147 in China.
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