Research Brief
What Is 5-Amino-1MQ?
Quick Answer
⚠️ Important: 5-Amino 1MQ is a small molecule (methylquinolinium derivative), not a peptide chain. It is an experimental research chemical — not FDA-registered, not GRAS, and banned by WADA (S0 category). 5-Amino 1MQ (5-amino-1-methylquinolinium, CAS 42464-96-0) is a synthetic small molecule classif...
⚠️ Important: 5-Amino 1MQ is a small molecule (methylquinolinium derivative), not a peptide chain. It is an experimental research chemical — not FDA-registered, not GRAS, and banned by WADA (S0 category).
5-Amino 1MQ (5-amino-1-methylquinolinium, CAS 42464-96-0) is a synthetic small molecule classified as a methylquinolinium derivative. [1] It was developed by Dr. Stanley J. Watowich’s research group at the University of Texas Medical Branch (UTMB) at Galveston as a selective inhibitor of the metabolic enzyme nicotinamide N-methyltransferase (NNMT). [2]
5-Amino 1MQ is an analogue of the parent molecule 1-methylquinolinium (1-MQ), modified with a primary amine substitution at the 5-position of the quinoline ring. This structural modification was rationally designed to optimize binding affinity to NNMT while dramatically improving membrane permeability — a critical limitation of the parent 1-MQ molecule. [3]
In conditions such as obesity, type 2 diabetes, and aging, NNMT is overexpressed in adipose tissue and skeletal muscle, where it depletes cellular pools of NAD+ and SAM. By blocking NNMT, 5-Amino 1MQ preserves these critical metabolic cofactors, shifting cellular metabolism from fat storage to fat oxidation and energy expenditure. [4]
Regulatory Status:
- FDA: NOT registered for human use — experimental research chemical. [5]
- WADA: Banned under S0 category (Non-Approved Substances) — prohibited at all times.
- GRAS: Not classified as Generally Recognized as Well-tolerated for dietary supplementation.
Developer: Ridgeline Therapeutics (Houston, TX), founded by Dr. Watowich, is advancing a lead NNMT inhibitor candidate (RT-002) toward Phase 1 first-in-human clinical trials, with IND-enabling GLP toxicology studies in minipigs currently underway. [6]
Pharmacokinetic Highlights:
- Oral Bioavailability: 38.4% (rats) [7]
- Half-Life: ~6.9 hours (oral), ~3.8 hours (IV) in rats
- Cmax: 2,252 ng/mL (oral, rats)
- Membrane Permeability: High (passive and active transport)
References
- Neelakantan H, Wang HY, Vance V, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015–5028, 2017.
- Neelakantan H, Brightwell CR, Graber TG, et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol, 147, 141–152, 2018.
- Neelakantan H, Vance V, Wetzel MD, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem, 60(12), 5015-5028, 2017.
- Sun WD, Zhu GY, Li J, et al. Nicotinamide N-methyltransferase (NNMT): a novel experimental target for metabolic syndrome. Front Pharmacol, 15, 1410479, 2024.
- World Anti-Doping Agency (WADA). The World Anti-Doping Code International Standard: Prohibited List 2025. S0: Non-Approved Substances.
- Watowich SJ. SBIR Award: NNMT Inhibitor Development. National Institute on Aging (NIA), 2021.
- Awosemo O, Neelakantan H, Watowich SJ, et al. Development & Validation of LC–MS/MS Assay for 5-Amino-1-Methyl Quinolinium in Rat Plasma. J Pharm Biomed Anal, 204, 114255, 2021.
- Liu JR, Deng ZH, Zhu XJ, et al. Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes. BioMed Res Int, 2021, 9924314, 2021.
- Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition in obese mice. Sci Rep, 11(1), 5637, 2021.
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Sci Rep, 14(1), 15554, 2024.
- Neelakantan H, Vance V, Wang HYL, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol, 163, 481–492, 2019.
- Babula J, Dimet-Wiley AL, Seyoum B, et al. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab, 26(11), 5272–5282, 2024.
- Li XY, Pi YN, Chen Y, et al. Nicotinamide N-Methyltransferase: A Promising Biomarker and Target for Human Cancer Therapy. Front Oncol, 12, 894744, 2022.
- Moody TW, Nuche-Berenguer B, Jensen RT. Cancer and NNMT overexpression in aggressive tumors. Curr Opin Endocrinol Diabetes Obes, 2022.
- Dimet-Wiley A, Sampson CM, Neelakantan H, et al. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep, 12(1), 484, 2022.
- Dong G, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inhibition improves limb function in experimental peripheral artery disease. Acta Physiol, 2025.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 12,071,409, August 27, 2024.
- Watowich S, Neelakantan H, McHardy SF. Quinoline derived small molecule inhibitors of nicotinamide N-methyltransferase (NNMT) and uses thereof. U.S. Patent No. 11,401,243, August 2, 2022.
Related Research Questions
FOR RESEARCH USE ONLY
This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.