5-Amino-1MQ (NNMT inhibitor)
5-Amino-1MQ — the NNMT-inhibitor fat-loss compound: elegant mechanism, animal-only evidence

Class: small_molecule
Synonyms: 5-Amino-1MQ
5-amino-1-methylquinolinium (iodide)
5A1MQ
an NNMT inhibitor (NNMTi). INCI: none
Function tags: metabolic
fat loss (adipose-direct)
NAD⁺ / cellular energy
(preclinical:) muscle-stem-cell / aging
Overall evidence grade: C
WADA prohibited: no
Last updated: 2026-07-13

In brief: 5-Amino-1MQ is a small-molecule NNMT inhibitor (not a peptide) studied for fat loss through a mechanism quite different from GLP-1 drugs: instead of curbing appetite, it acts inside fat cells. NNMT normally consumes SAM (the cell's methyl donor) and pulls nicotinamide out of the NAD⁺ salvage pathway; inhibiting it raises SAM and NAD⁺, boosting sirtuin (SIRT1/3) activity, fat oxidation, thermogenesis and polyamine flux — and NNMT is expressed highest in adipose tissue, offering the theoretical appeal of a fat-targeted intervention. The preclinical evidence is genuinely interesting: in diet-induced obese mice, 5-Amino-1MQ reduced body weight, fat mass, adipocyte size (~30–40%) and total cholesterol (~30%) without changing food intake or lean mass, and a separate line showed muscle-stem-cell reactivation in aged mice. The decisive caveat: every efficacy result is in rodents or cell culture. There are no completed human trials, no published human pharmacokinetics, and no approval anywhere. Elegant mechanism, essentially no human proof.

## Identity a **small, orally-bioavailable molecule** (a quinolinium salt, not a peptide) engineered as a **selective, substrate-competitive inhibitor of nicotinamide N-methyltransferase (NNMT)** — an enzyme most highly expressed in **adipose (fat) tissue**. Its quinolinium ring mimics the nicotinamide substrate, letting it occupy NNMT's active site and block the methylation reaction. It appears in "peptide" catalogues because of the metabolic-medicine crowd it travels with, but chemically it belongs with the register's **non-peptide tier** (alongside MK-677, Orforglipron, Noopept). ## Mechanism (as proposed) NNMT (nicotinamide N-methyltransferase) sits at a metabolic crossroads. It **methylates nicotinamide** (using **SAM**, the universal methyl donor) to make 1-MNA — a reaction that both **burns SAM** and **removes nicotinamide from the NAD⁺ salvage pathway**. When NNMT is overactive (as it is in obese/aged adipose tissue), it **depletes NAD⁺ and SAM**. 5-Amino-1MQ **blocks NNMT's active site**, so both pools rise: more **NAD⁺** fuels **sirtuins (SIRT1/SIRT3)** → more fat oxidation, mitochondrial activity and energy expenditure; more **SAM** feeds **polyamine flux and histone methylation** that shift adipocytes toward **thermogenesis and away from fat storage**. Because NNMT is concentrated in fat tissue, the effect is relatively **tissue-targeted** — the theoretical selling point. The framing is "**cellular optimization**" (fixing a metabolic inefficiency inside the cell) rather than the "hormonal manipulation" of incretin drugs.

Evidence grades by outcome:
outcome: Fat loss / anti-obesity
grade: F
base: Neelakantan 2018 (DIO mice, ~/day): ↓body weight, ↓fat mass, ↓adipocyte size, no change in food intake; target-validated by Kraus 2014 (genetic knockdown, Nature)
caveat: Compelling but rodent-only; "no change in food intake" is a genuinely interesting mechanistic point, but it's still animals. No human efficacy
outcome: NNMT as an obesity target (validation)
grade: C
base: Kraus 2014 Nature (knockdown) + human adipose NNMT-expression correlations (Kannt 2015)
caveat: The target is well-validated (including some human correlational data); the drug is not — don't conflate them
outcome: Muscle stem cells / aging / recomposition
grade: F
base: Neelakantan 2019 (aged mice: stem-cell reactivation, ~70% peak-torque gain)
caveat: Aged-mouse only; intriguing "recomp" angle but no human data
outcome: Lipids / insulin sensitivity
grade: F
base: Mouse: ~30% lower total cholesterol; Kraus/Brachs: improved insulin sensitivity (glucose tolerance less consistent)
caveat: Preclinical; specific LDL / clinical-lipid effects not established
outcome: Human efficacy or safety (any use)
grade: F
base: None — no completed human trials, no published PK
caveat: The defining gap: bioavailability, half-life, dosing, safety in humans are all unknown
outcome: Safety (animal)
base: Short rodent studies: "no observable toxicity" over ~11 days
caveat: Reassuring in mice over days; says nothing about human safety or chronic use

Legal status:
region: EU
status: Not FDA-approved (gray-market)
note: not approved anywhere; investigational research chemical. Not a cosmetic; not on the FDA 503A bulk-compounding list (no legitimate compounding/clinical access route). Sold as a "research use only" small molecule.

Cosmetic claims:

Note: The "cellular optimization" fat-loss molecule — mechanistically elegant, entirely animal-tested. Three points define this entry: (1) it is not a peptide — a small-molecule enzyme inhibitor, expanding the register's non-peptide tier; (2) it works by a genuinely different route from GLP-1 drugs — directly on fat cells (inhibiting the enzyme NNMT), not by suppressing appetite; (3) the preclinical story is compelling and well-cited — but there is zero completed human data, so the honest grade is capped low despite the elegant mechanism.
Status note: watch for first-in-human PK/efficacy trials — that would be the first thing to move any grade off F

Sources:
Kraus D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508:258-262 (target validation; genetic, not 5A1MQ).
Neelakantan H, et al. Selective and membrane-permeable small-molecule NNMT inhibitors reverse high-fat-diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141-152 (the defining 5-Amino-1MQ paper).
Neelakantan H, et al. Small-molecule NNMT inhibitor activates muscle stem cells and improves muscle regeneration in aged mice. Biochem Pharmacol. 2019 (muscle branch).
Kannt A, et al. NNMT mRNA in human adipose tissue and plasma 1-MNA with insulin resistance. Diabetologia. 2015 (human correlational).
Brachs S, et al. (2019) — genetic NNMT loss, insulin sensitivity. Note: no human interventional PK/efficacy data published as of 2026.