Chemical form. Exists only as a salt — most commonly the iodide (CAS 42464-96-0, PubChem CID 66522933), a light orange crystalline powder; the free base (the cation without a counter-ion, PubChem CID 950107, CAS 685079-15-6) does not exist as a standalone substance.
Mechanism of action. NNMT is a cytosolic enzyme that transfers a methyl group from S-adenosylmethionine (SAM) to nicotinamide, forming 1-methylnicotinamide (1-MNA) and removing nicotinamide from the NAD⁺ salvage pathway. 5-Amino-1MQ binds at the NNMT substrate site (IC₅₀ = 1.2 μM) selectively: according to patent US11,401,243 B2, even at concentrations up to 600 μM (500 times the IC₅₀) the compound has essentially no effect on the related methyltransferases DNMT1, PRMT3, and COMT, or on the NAD⁺ salvage-pathway enzymes NAMPT and SIRT1.
NAD⁺, SAM, and sirtuins. Blocking NNMT both spares nicotinamide for NAD⁺ resynthesis and preserves SAM for methylation reactions. In adipocyte culture the compound raises intracellular NAD⁺ 1.2-1.6-fold and lowers 1-MNA by up to 60% (at 1-60 μM). The rise in NAD⁺ activates SIRT1 and AMPK — unlike NAD⁺ precursors (NMN, NR), which simply add raw material, the mechanism here is conservational: less nicotinamide is wasted down the side pathway.
Research profile. The most striking results come from muscle-tissue studies: in aged mice the compound raised peak tibialis anterior torque by roughly 70% and nearly doubled muscle fiber cross-sectional area, while combined with exercise the gain in grip strength reached 60% (versus 40% without exercise). With chronic dosing over 28 days, fat mass gain was suppressed by roughly 72%; in the classic diet-induced-obesity model, plasma cholesterol dropped by about 30% with no change in food intake. The compound also protects endothelial cells from oxidative stress and has an oral bioavailability of 38.4% in rats. Detailed results with links to the primary sources are in the research table below.
Research stage. This remains a preclinical compound: all data reported here come from cell culture and animal models, and no completed human studies have been published. Its core pharmacological properties — selectivity, dose-response, pharmacokinetics — are already well characterized preclinically; that is a typical stage for a compound synthesized and optimized since 2017.
Evidence base
All available research on 5-Amino-1MQ
Compound discovery: IC50 approx. 1 uM, >1000-fold potency range
Compound design
In vitro
· Screening of quinolinium/isoquinolinium/pyridinium/benzimidazolium analogues + docking · Neelakantan et al. , J Med Chem 60(12):5015-5028 , USA , 2017 Q1
Screening of over a thousand NNMT-inhibitor analogues on a quinolinium scaffold identified compounds ranging from nanomolar to millimolar IC50 - a greater than 1000-fold spread of potency across the series. This work laid the structural foundation from which 5-Amino-1MQ was later optimized.
Key efficacy study: -5.1% body weight, -35% fat mass, no change in appetite
Diet-induced obese mice lost approximately 5.1% body weight and 35% fat mass, with adipocyte size reduced by more than 30% and lower plasma cholesterol - all without changes in food intake or overt adverse effects. Lean mice did not lose significant weight.
Pharmacokinetics: 38.4% oral bioavailability
Pharmacokinetics
Rats (Sprague-Dawley)
· LC-MS/MS assay validation, oral and IV · Awosemo, Neelakantan et al. , J Pharm Biomed Anal 204:114255 , USA , 2021
Oral bioavailability of 38.4%, Cmax of 2252 ng/mL after oral dosing, half-life of 6.9 hours orally and 3.8 hours intravenously. High passive membrane permeability (PAMPA >150 nm/s) - unusually favorable for a quaternary ammonium compound.
+70% muscle strength and nearly doubled fiber cross-sectional area in aged mice
Muscle regeneration
Mice (24 mo.) + in vitro C2C12
· Muscle injury, doses of 5 and 10 mg/kg · Neelakantan et al. , Biochem Pharmacol 163:481-492 , USA , 2019
In aged mice after muscle injury, NNMT inhibition raised peak tibialis anterior torque by roughly 70% and nearly doubled fiber cross-sectional area compared with controls - activation of senescent muscle stem cells.
Protects endothelium against oxidative stress
Vascular protection
In vitro
· HAEC, HMEC-1, EA.hy926, menadione-induced stress · Campagna et al. , Biochim Biophys Acta Mol Cell Res 1868:119082 , USA , 2021
Suppressing NNMT with the compound (labeled "5MQ") or with shRNA protected three different endothelial cell lines from oxidative-stress-induced damage (menadione) - the first evidence of a protective role beyond adipose and muscle tissue.
Combined with diet: p<0.0001 for weight and fat, enhanced liver effects
Diet synergy
Mice (DIO)
· Compound + switch to reduced-calorie diet, n=6-8/group · Sampson, Dimet et al. , Sci Rep 11(1):5637 , USA , 2021 Q1
Combining NNMT inhibition with a switch to a reduced-calorie diet significantly lowered body weight and fat mass (both p<0.0001) beyond either intervention alone. It also reduced liver fat content (p=0.0034), total liver weight (p=0.0011), and both microvesicular (p=0.0425) and macrovesicular (p=0.0039) hepatic steatosis.
Anti-proliferative activity in HeLa cells
Oncology context
In vitro
· HeLa cell line (cervical cancer), 0.1-500 uM · Akar et al. , J Obstet Gynaecol , Turkey , 2021
Across a concentration range of 0.1-500 uM, the compound (labeled "5MQ") suppressed HeLa cell proliferation - a signal that NNMT inhibition may have relevance beyond the metabolic context, though this remains the only oncology study of the compound to date.
Combining NNMT inhibition with calorie reduction produced a gut microbiome profile distinct from both control and diet-alone groups. Specific taxa or diversity indices were not reported in the available summary of this study.
Chronic 28-day dosing: -72% fat mass gain
Chronic dosing
Mice (DIO)
· 32 mg/kg/day, 28 days, PK and tissue distribution · Babula et al. , Diabetes Obes Metab 26(11):5272-5282 , USA , 2024
With daily dosing for 28 days, fat mass gain was suppressed by roughly 72% relative to control, glucose tolerance improved, and plasma cholesterol decreased. Accumulation of the compound in adipose tissue is consistent with its lipophilic profile - chronic administration was well tolerated.
Grip strength: +40% alone, +60% combined with exercise
In sedentary aged mice, the compound alone increased grip strength by roughly 40% versus control; combined with exercise, the gain reached approximately 60% - indicating the effect does not merely mimic exercise but potentiates it.
Reference
Official facts about 5-Amino-1MQ
Mechanism of action
Selective inhibitor of nicotinamide N-methyltransferase (NNMT, IC₅₀ 1.2 μM). Raises intracellular NAD⁺ 1.2–1.6-fold and lowers 1-methylnicotinamide by up to 60% (in vitro).
International clinical status
Not approved by the FDA or EMA. No completed or published human clinical trial has been conducted — the entire evidence base (efficacy in obesity, effects on muscle stem cells) comes from mice and cell culture studies. No IND application appears in the public registry.
Clinical status in Ukraine
Not registered as a medicine; not listed in Ukraine's State Register of Medicinal Products (drlz.com.ua).
Cannot be registered or legally sold as a supplement or weight-loss product for human use, in any country. In the US it is already used by some clinics outside of clinical-trial protocols, despite having no FDA approval of any kind.
Only legal form of sale
Research chemical, laboratory reagent — not for human consumption.
Patent status
An active US patent, US11,401,243 B2 (filed 2018, granted 2022, anticipated expiration 2038), owned by The Board of Regents of the University of Texas System, covers a class of quinoline-derived NNMT inhibitors and methods of use (obesity treatment, muscular therapy, and others); 5-Amino-1MQ is explicitly among the compounds tested in the patent.
Does not require deep-freezing
The powder (iodide salt) is a crystalline quaternary ammonium salt — this class of compounds is generally chemically stable in air and humid conditions, so deep-freezing is not a strict requirement. The manufacturer (Selleck) confirms 3 years at -20°C, but an ordinary refrigerator (2-8°C, dry, dark) is enough for a working supply — freezing is only needed for long-term archival storage. Unlike the powder, the solution is far less stable: up to a year at -80°C and only about a month at -20°C.
Solubility: moderate in water
5-7 mg/mL in water — the permanent positive charge on the quaternary ammonium nitrogen gives better hydrophilicity than neutral aromatic compounds. Solubility in DMSO is much higher (about 57 mg/mL), while ethanol solubility is low (3-6 mg/mL) (per Selleck Chemicals).
For research use only. This product is not a medicine, food supplement or cosmetic. Not intended for human or animal use. Sold to persons aged 18+.
