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

1. www.aasraw.com 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 1 aas15@aasraw.com

2. www.aasraw.com disease progression in symptomatic animals as demonstrated in these studies. J147 Technical Data Name J147,J-147 CAS 1146963-51-0 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 Synonyms 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 mide, a phenyl hydrazide compound that has been shown to prevent memory defici 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 Descriptio n Application Implicated in Alzheimer's disease Molecular Formula C18H17F3N2O2 Molecular Weight 350.3349896 Melt Point 177-178°C Appearanc e White or off-white, light yellow powder 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 2 aas15@aasraw.com

3. www.aasraw.com 7℃ for long term (months to years). Brief www.aasraw.com Purity >=99.8% MSDS Inquire Package 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? 3 aas15@aasraw.com

4. www.aasraw.com 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, 4 aas15@aasraw.com

5. www.aasraw.com 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 workwithin 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 5 aas15@aasraw.com

6. www.aasraw.com 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 modified version of a molecule found in curcumin, 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 6 aas15@aasraw.com

7. www.aasraw.com 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 7 aas15@aasraw.com

8. www.aasraw.com 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 8 aas15@aasraw.com

9. www.aasraw.com 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. 9 aas15@aasraw.com

10. www.aasraw.com -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. 10 aas15@aasraw.com

11. www.aasraw.com -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). 11 aas15@aasraw.com

12. www.aasraw.com 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. 12 aas15@aasraw.com

13. www.aasraw.com 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. 13 aas15@aasraw.com

14. www.aasraw.com 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. 14 aas15@aasraw.com

15. www.aasraw.com 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. 15 aas15@aasraw.com