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5-Amino-1MQ (60 Capsules)

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5-Amino-1MQ (60 Capsules)

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5-amino-1MQ is a small molecule that blocks the activity of the enzyme called nicotinamide N-methyltransferase (NNMT). NNMT is a very important component in metabolism and energy and is predominantly active in fat tissue. By blocking NNMT, 5-amino-1MQ stimulates an increase in nicotinamide adenine dinucleotide (NAD+), a cofactor that is central to cellular metabolism, thereby increasing metabolic rate and activating a gene called sirtuin-1 (SIRT1). SIRT1 is also known as the "longevity gene" because of its role in reducing the risk of diabetes, obesity, metabolic syndrome, atherosclerosis and other forms of cardiovascular disease, kidney disease, liver disease, neurodegeneration, and cancer. Research in mice given 5-amino-1MQ showed a 7% reduction in body mass over 10 days without any changes in food intake, compared to controls. Research has shown that decreasing NNMT may help shrink fat cells and reduce the size of fat deposits.

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Product Usage: This PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. All product information available on this website is for educational purposes only. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals. This product is not a drug, food, or cosmetic and may not be misbranded, misused or mislabled as a drug, food or cosmetic.

5-Amino-1MQ Overview

5-amino-1MQ (5-amino-1methylquinolinium) an analogue of methylquinolinium, is a short peptide inhibitor of cytosolic nicotinamide N-methyltransferase (NNMT). The NNMT enzyme has been linked to both obesity and type 2 diabetes and is known to play a role in energy homeostasis within the cell. Inhibiting NNMT leads to significant weight loss, decreased fat mass and fat cell (adipocyte) size, and lower plasma cholesterol and glucose levels. 5-amino-1MQ and other methylquinolinium derivatives are under active investigation as potential treatments for obesity and diabetes. It also appears that inhibition of NNMT can activate stem cells and improve regenerative capacity in skeletal muscle.

5-Amino-1MQ Structure

Molecular Formula: C10H11N2
Molecular Weight: 159.21 g/mol
PubChem CID: 950107
CAS Number: 42464-96-0
Synonyms: 5-amino-1-methylquinolinium

Structure

Source: PubChem

5-Amino-1MQ Research

Obesity

Nicotinamide N-methyltransferase is a cytosolic enzyme found in many cells throughout the body, but is most abundant in liver and fat cells. Research in mice shows that high levels of NNMT are associated with decreased levels of the sugar transporter GLUT4. GLUT4, which is primarily in striated muscle (skeletal and cardiac) and fat cells, is heavily linked to blood sugar levels and the development of diabetes. In rodent studies, mice that produce high levels of GLUT4 are insulin sensitive and relatively resistant to the development of type 2 diabetes while mice with low GLUT4 levels demonstrate profound insulin resistance.

In fact, GLUT4 has been linked to basal metabolic rate and the concepts of fast and slow metabolism. Individuals with naturally high levels of GLUT4 have “faster metabolism” than those with low levels of GLUT4 and burn more calories as a result. It is also true that production of the transporter is stimulated by exercise, explaining why exercise can help to combat weight loss, elevated blood sugar levels, and insulin resistance. As it turns out, GLUT4 and NNMT are closely linked to one another and to basal metabolism in mammals [1]. According to Dr. Barbara Kahn of Harvard Medical School, the connection between GLUT4 and NNMT is what first led to the investigation of the latter enzyme as a potential target in the treatment of diabetes and obesity. High levels of NNMT are often found in the fat cells of animals with insulin resistance. Manipulating this gene helps to counteract insulin resistance and thus diabetes. It also has a profound effect on weight and obesity.

Human metabolism, and indeed all animal metabolism is highly efficient, making the most use out of a limited number of calories. Unfortunately, this very efficiency may be the mechanism underlying our penchants for obesity in the setting of excess calorie intake. Reducing the efficiency of human metabolism, causing the body to essentially waste calories, has long been a holy grail of medicine as it works to combat the growing obesity epidemic. NNMT and its interactions with GLUT4 may be the link that scientists have been searching for. [2], [3].

In the most basic sense, NNMT slows how quickly the body utilizes calories thereby leaving them available for storage in fat or glycogen. Decreased NNMT levels decrease the conversion of nicotinic acid (NA) into 1-methylnicotinamide (1-MNA). This process has two effects on metabolism as follows.

Weight

Source: Science Direct

So the net result of administering an NNMT blocker like 5-amino-1MQ is an increase in energy burning and a decrease in energy storage. When this is coupled with the fact that decreased NNMT levels also increases GLUT4 transporter expression, you have a recipe for improve glucose clearance from the blood and then direct disposition of that glucose when it is burned. The results are decreased need for insulin, decreased insulin resistance, decreased fat production, and increased energy metabolism. Studies in mice over just 10 days of 5-amino-1MQ administration reveal a 7% reduction in rate and a 30% reduction in fat mass. In addition, blood cholesterol levels in treated mice are equal to those of non-obese mice. Remarkably, these changes occur without any alteration in food consumption [5]. Mice given 5-amino-1MQ show a 7% reduction in body mass over just 10 days, without any changes in food intake, compared to controls:

Weight

Source: Science Direct

More recent evidence suggests that the benefit of 5-amino-1MQ may extend beyond its ability to downregulate NNMT and thus increase inefficient metabolism and GLUT4 expression. Research in mice suggests that by boosting GLUT4 expression, 5-amino-1MQ may alter the way fat cells work, leading them to produce an alternative class of lipids that have anti-diabetic and anti-inflammatory effects. This class of lipids, known as PAHSAs (palmitic acid esters of hydroxy-stearic acids), can reduce insulin resistance on their own and reduce inflammation leading to improved risk profiles for events like heart attack and stroke [6]. Those this aspect of 5-amino-1MQ is relatively new, it hints at an extended benefits profile for this already remarkable molecule.

5-Amino-1MQ and Muscle Function

The impact of 5-amino-1MQ on skeletal muscle is multifaceted. Much like in adipose tissue, the presence of 5-amino-1MQ in muscle promotes the production of the GLUT4 receptor and boosts the inefficiency of metabolism leading to increased energy burn. Recent research in mice, however, suggests that inhibiting NNMT in any way, including with 5-amino-1MQ, may actually boost muscle repair by stimulating stem cells.

Research in 24-month-old mice (old for mice) reveals that those treated with an NNMT inhibitor experience substantial stem cell activation in muscle tissue, following injury, compared to controls. These mice exhibit myofibers that are 2-fold larger in cross section and have greater contractile strength. In fact, mice treated with NNMT inhibitors have 70% more contractile force in healed muscle than control mice [7]. The benefits of boosting muscle stem cell production go well beyond simply accelerating rates of repair following injury. Stimulating stem cells could help elderly people maintain their independence for much longer. By improving mobility and reducing the risk of things like falls, NNMT inhibitors could substantially improve quality of life and levels of independent living among older adults.

There is also evidence that increased NNMT expression is a common feature of muscle wasting disorders such as Duchenne Muscular Dystrophy and that reducing NNMT levels may help to alleviate the symptoms of some of these conditions [8]. This, again, is tied in to the ability of NNMT to inhibit stem cell growth and division. By reducing NNMT levels, compounds like 5-amino-1MQ may provide benefit in a variety of muscle-wasting conditions.

The exact effects of NNMT inhibition on muscle function are not fully understood, but another component appears to relate to NAD+ levels. Recall that NNMT inhibition results in increased levels of NAD+. By replenishing NAD+ levels via NNMT inhibition, compounds like 5-amino-1MQ have been shown to improve muscle function, heart pathology, and DMD in animal models. It appears that improvement in mitochondrial function combined with decreases in inflammation and fibrosis, all related to increases in NAD+ levels, are the main drivers of these benefits [9].

A Possible Role for 5-Amino-1MQ in Cognition

NAD+ is a critical compound in brain energy homeostasis. Depletion of NAD+ has been linked to a number of cognitive conditions, but is known to impact communication at the synaptic junction of neurons and at the neuromuscular junction where nerves connect to muscle tissue. Research in mice suggests that decreases in NAD+ levels can reduce synaptic transmission, impair muscle function, and impact overall cognitive function [10]. Though 5-amino-1MQ has not been specifically tested in this setting, there is good reason to believe that the compound will have the same effect on NAD+ levels in the brain as it has elsewhere. This means that it could be used not just as a treatment for cognitive dysfunction, but as a potential nootropic to boost cognitive function in the average individual. Whether this bears out in research remains to be seen, but there is active interest in the potential cognitive benefits of 5-amino-1MQ.

NNMT and Cancer

There is significant research to suggest that NNMT expression is increased in gastric cancers of all types as well as pancreatic cancer, renal cell carcinoma, and bladder cancer. Mice without the NNMT gene so resistance to the development of these cancers, suggesting a causal role for NNMT. Though the research is still in progress, there is some speculation that inhibition NNMT may be a way to both treat and prevent certain types of cancer or, at the very least, reduce how aggressive certain cancer are[8]. It remains to be seen whether 5-amino-1MQ, by reducing NNMT function, will have any effect on the various cancers mentioned.

5-Amino-1MQ Summary

5-amino-1MQ is a small, membrane permeable analogue of naturally occurring methylquinolinium. It has been shown, in animal models to inhibit expression of the enzyme nicotinamide N-methyltransferase. NNMT is an important component of cellular energy metabolism and has been linked heavily to weight control and insulin resistance. Studies show that inhibiting NNMT with 5-amino-1MQ can lead to weight reduction, resistance to diabetes, and improved plasma cholesterol levels. There is also good evidence to show that NNMT inhibition can help to regulate muscle and nerve cell function and there is some hope that compounds like 5-amino-1MQ may play a role in the treatment of conditions like muscular dystrophy and the muscle wasting that results from age. Reductions in levels of NNMT have been linked to reduced aggressiveness in several different varieties of cancer.

Article Author

The above literature was researched, edited and organized by Dr. E. Logan, M.D. Dr. E. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Scientific Journal Author

Barbara B. Kahn is chief of the Division of Endocrinology, Diabetes, and Metabolism at Beth Israel Deaconess Medical Center (BIDMC) and the George Richards Minot Professor of Medicine at Harvard Medical School. She is an internationally recognized scientist in the area of obesity and type 2 diabetes, and her lab investigates the molecular mechanisms underlying these conditions, including the regulation of insulin action, food intake, and energy balance. Kahn received BA and MD degrees from Stanford University and an MS from the University of California at Berkeley. After completing internal medicine training at the UC Davis Medical Center, she began her career in molecular research at the National Institutes of Health. Kahn has received numerous awards including the Outstanding Scientific Achievement Award from the American Diabetes Association; the H. C. Jacobaeus Prize from the Novo Nordisk Foundation and the Karolinska Institutet; the Charles H. Best Lectureship and Award from the University of Toronto; and the Gerald D. Aurbach Award Lecture from the Endocrine Society. Kahn was elected to the Institute of Medicine of the National Academies and is a fellow of the American Association for the Advancement of Science.

Barbara B. Kahn is being referenced as one of the leading scientists involved in the research and development of 5-Amino-1MQ. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Barbara B. Kahn is listed in [2] and [6] under the referenced citations.

Referenced Citations

  1. Y.-B. Kim et al., “Muscle-Specific Deletion of the Glut4 Glucose Transporter Alters Multiple Regulatory Steps in Glycogen Metabolism,” Mol. Cell. Biol., vol. 25, no. 21, pp. 9713–9723, Nov. 2005, doi: 10.1128/MCB.25.21.9713-9723.2005.
  2. E. Carvalho, K. Kotani, O. D. Peroni, and B. B. Kahn, “Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle,” Am. J. Physiol. Endocrinol. Metab., vol. 289, no. 4, pp. E551-561, Oct. 2005, doi: 10.1152/ajpendo.00116.2005.
  3. “Weight loss without effort: NNMT inhibitors,” Recherche animale. https://www.recherche-animale.org/en/weight-loss-without-effort-nnmt-inhibitors (accessed Mar. 30, 2020).
  4. N. Minois, D. Carmona-Gutierrez, and F. Madeo, “Polyamines in aging and disease,” Aging, vol. 3, no. 8, pp. 716–732, Aug. 2011.
  5. H. Neelakantan et al., “Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice,” Biochem. Pharmacol., vol. 147, pp. 141–152, Jan. 2018, doi: 10.1016/j.bcp.2017.11.007.
  6. P. M. Moraes-Vieira, A. Saghatelian, and B. B. Kahn, “GLUT4 Expression in Adipocytes Regulates De Novo Lipogenesis and Levels of a Novel Class of Lipids With Antidiabetic and Anti-inflammatory Effects,” Diabetes, vol. 65, no. 7, pp. 1808–1815, Jul. 2016, doi: 10.2337/db16-0221.
  7. H. Neelakantan et al., “Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle,” Biochem. Pharmacol., vol. 163, Feb. 2019, doi: 10.1016/j.bcp.2019.02.008.
  8. P. Pissios, “Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme,” Trends Endocrinol. Metab. TEM, vol. 28, no. 5, pp. 340–353, May 2017, doi: 10.1016/j.tem.2017.02.004.
  9. D. Ryu et al., “NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation,” Sci. Transl. Med., vol. 8, no. 361, p. 361ra139, Oct. 2016, doi: 10.1126/scitranslmed.aaf5504.
  10. S. Lundt, N. Zhang, X. Wang, L. Polo-Parada, and S. Ding, “The effect of NAMPT deletion in projection neurons on the function and structure of neuromuscular junction (NMJ) in mice,” Sci. Rep., vol. 10, Jan. 2020, doi: 10.1038/s41598-019-57085-4.

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The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body.  These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease.  Bodily introduction of any kind into humans or animals is strictly forbidden by law.

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Your Agreement to Abide by All Applicable Laws

By using this Web Site you agree to comply with any and all local, state, or federal laws, statutes, and regulations that relate in any manner to the use of this Web Site and the associated services or products contained thereon.

Relationship between www.PeptideSciences.com and Users.

www.PeptideSciences.com and users of our Site are independent contractors, and no agency, partnership, employment or other relationship is created or is intended to be created by the use of our Web Site.

Governing Law and Jurisdiction

This Web Site (excluding linked sites, if any) is administered and controlled by www.PeptideSciences.com and its affiliates, subsidiaries, officers, directors, employees or agents from its offices in the accordance with the laws of Nevis. You agree that this Terms and Conditions of Use Agreement and this Web Site will be governed by and construed in accordance Nevis law without giving effect to any principles of conflicts of laws. You access this Web Site and/or associated services of www.PeptideSciences.com at your own risk, and remain responsible for complying with the laws of the jurisdiction within which you are located.

Prices; Payment Terms; Interest

The prices for the products and services on this Web Site are quoted, for convenience, in United States dollars and shall be as set forth in this Web Site as at the time of acceptance of an order by www.PeptideSciences.com. Prices for Products shall be subject to change without any further notice. Credit terms are within www.PeptideSciences.com's sole discretion, and unless otherwise specified in www.PeptideSciences.com's invoice, payment must be received by www.PeptideSciences.com prior to www.PeptideSciences.com's acceptance of an order.

Consequences

www.PeptideSciences.com reserves the right to suspend or terminate your account if you violate the Terms of Use Agreement. If your violation causes harm to others, you agree to indemnify and hold www.PeptideSciences.com harmless from and against any and all loss, damage, or expense. If any dispute arises between us regarding this Agreement or your use of this Web Site, it shall be resolved through good faith negotiations between the parties.

Entire Agreement

These Terms and Conditions and any terms incorporated or referred to herein constitute the entire agreement between www.PeptideSciences.com and you relating to your use of this Web Site and the subject matter hereof, and supersede any prior understandings or agreements (whether electronic, oral or written) regarding the subject matter, and may not be amended or modified except in writing, or by www.PeptideSciences.com making such amendments or modifications in accordance with this Terms and Conditions of Use Agreement.

Severability

If any part of this Terms and Conditions of Use Agreement is deemed or determined to be unenforceable, then such part shall be eliminated or limited to the minimum extent necessary. The remainder of this Terms and Conditions of Use Agreement, including any revised portion, shall remain and be in full force and effect. This Terms and Conditions of Use Agreement are the entire agreement between us governing your use of this Web Site.

Headings

The headings contained in this Terms and Conditions of Use Agreement and the www.PeptideSciences.com Privacy Policy are for reference only.

Force Majeure

www.PeptideSciences.com shall not be liable for any delay or failure in performance caused by circumstances beyond its reasonable control, including, without limitation, delays due to backorders of requested products, mail delays, customs delays or lost shipments. www.PeptideSciences.com shall not be responsible to notify the Customer in the event of such delays. The Customer shall be solely responsible to make other arrangements to purchase alternative products and any costs incurred in connection with such purchases.

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Complete Agreement

Except as expressly provided in a particular "legal notice" on this Site, these Terms and Conditions constitute the entire agreement between you and this Site with respect to the use of this Site, and Content. By clicking “I agree” when placing your order, you agree with ALL OF OUR TERMS and CONDITIONS as stated above as well as our Shipping and refunds Policy.

Thank you for your cooperation.