5-Amino-1MQ
A selective NNMT inhibitor that reduces fat mass by boosting NAD+ and cellular energy expenditure — without affecting appetite. In mice, 11 days of treatment produced 5% weight loss and 35% reduction in white adipose tissue.
What is 5-Amino-1MQ?
5-Amino-1MQ is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme that drains the body's NAD+ supply by methylating nicotinamide. NNMT is overexpressed in white adipose tissue of obese individuals, creating a metabolic bottleneck that promotes fat storage. By blocking NNMT, 5-Amino-1MQ preserves cellular NAD+ levels, increases energy expenditure, and shifts metabolism away from fat storage — all without reducing food intake. In diet-induced obese mice, 11 days of treatment produced 5.1% body weight loss and a 35% reduction in white adipose tissue mass with over 40% smaller adipocytes. It is technically not a peptide but a quinolinium derivative, widely discussed in the peptide and metabolic optimization community. The foundational NNMT-obesity connection was published in Nature (2014).
What 5-Amino-1MQ Is Investigated For
5-Amino-1MQ is primarily investigated for fat loss through a non-appetite-suppressing mechanism — NNMT inhibition that preserves cellular NAD+ and increases energy expenditure in adipocytes. The strongest evidence comes from a single 11-day mouse study showing 5% body weight loss, 35% reduction in white adipose tissue, and 30% lower cholesterol without any change in food intake, backed by the foundational 2014 Nature paper establishing NNMT's role in obesity. No human clinical trials have been published — every human dose, safety claim, and outcome expectation is extrapolation from rodent data. Secondary interest centers on NAD+ preservation for longevity and theoretical synergy with NMN or NR, but those combinations are mechanistically rational rather than clinically validated. The honest framing is strong preclinical rationale for a specific obesity mechanism, zero human trial data, and important open questions about the oncological implications of chronic NNMT inhibition.
History & Discovery
5-Amino-1MQ emerged from chemistry programs targeting nicotinamide N-methyltransferase (NNMT), an enzyme whose role in obesity was established by a 2014 Nature paper from the lab of Barbara Kahn at Beth Israel Deaconess. That foundational paper showed that NNMT knockdown protected mice from diet-induced obesity by increasing energy expenditure and shifting cellular metabolism — establishing NNMT inhibition as a credible target for fat loss without appetite suppression. 5-Amino-1-methylquinolinium was characterized in subsequent medicinal chemistry work as a small-molecule, membrane-permeable, selective NNMT inhibitor that increases intracellular NAD+ and SAM levels by blocking nicotinamide methylation. The headline preclinical paper (Neelakantan et al.) showed that 11 days of subcutaneous 5-amino-1MQ in diet-induced obese mice produced 5.1% weight loss, 35% reduction in white adipose tissue mass, and 30% lower cholesterol — without altering food intake. The compound has subsequently moved into the longevity and metabolic-optimization market through compounding pharmacies and research-chemical suppliers, well in advance of any human clinical trial. Note that 5-amino-1MQ is a small molecule (a quinolinium derivative), not a peptide — it is included on this site because it is widely discussed alongside metabolic peptides in the optimization community.
How It Works
Your body has an enzyme called NNMT that breaks down a molecule needed for cellular energy (NAD+). In obese people, NNMT is overactive in fat tissue, draining NAD+ and slowing metabolism. 5-Amino-1MQ blocks this enzyme, preserving NAD+ levels. With more NAD+ available, fat cells burn more energy — leading to fat loss without needing to eat less.
5-Amino-1MQ is a selective, membrane-permeable inhibitor of nicotinamide N-methyltransferase (NNMT). NNMT catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to nicotinamide, generating 1-methylnicotinamide (1-MNA) and consuming both SAM and NAD+ precursors. In white adipose tissue, NNMT overexpression in obesity creates a metabolic drain: reduced NAD+ impairs oxidative metabolism, and reduced SAM impairs polyamine flux, both favoring fat storage. 5-Amino-1MQ inhibition reverses this: it increases intracellular NAD+ and SAM, upregulates polyamine metabolism enzymes (ODC, SSAT, PAO), increases GLUT4 transporter expression, and enhances oxygen consumption in adipocytes. In diet-induced obese mice (11 days, 20 mg/kg x3/day SC), it produced 5.1% weight loss (vs 1.4% gain in controls), 35% reduction in epididymal white adipose tissue mass, >40% reduction in adipocyte volume, and 30% lower total cholesterol — all without altering food intake. The compound shows high selectivity, not inhibiting related SAM-dependent methyltransferases or NAD+ salvage pathway enzymes.
Evidence Snapshot
Human Clinical Evidence
None. No human clinical trials have been published for 5-Amino-1MQ. The compound is used off-label through compounding pharmacies but without clinical trial support.
Animal / Preclinical
Moderate. The key study demonstrated 5.1% weight loss, 35% WAT reduction, and 30% lower cholesterol in 11 days in DIO mice without altering food intake. The foundational Nature paper (2014) established NNMT knockdown as protective against diet-induced obesity via increased energy expenditure. Additional studies show reduced calorie diet combined with NNMT inhibition establishes a distinct beneficial microbiome.
Mechanistic Rationale
Strong. NNMT's role in obesity is well-validated (Nature, 2014). The NAD+/SAM/polyamine mechanistic cascade is well-characterized. 5-Amino-1MQ's selectivity for NNMT over related enzymes is confirmed. The absence of appetite effects (pure metabolic mechanism) is consistently demonstrated.
Research Gaps & Open Questions
What the current literature has not yet settled about 5-Amino-1MQ:
- 01Human pharmacokinetics, oral bioavailability, dosing, and safety are entirely uncharacterized — no published Phase 1 trial exists.
- 02Long-term oncological implications of chronic NNMT inhibition — given NNMT's documented roles in cancer biology (variably tumor-promoting or tumor-suppressing depending on context), multi-year human exposure carries unquantified risk.
- 03Whether metabolic effects observed in 11-day mouse studies translate to clinically meaningful body composition or metabolic outcomes in humans is unproven.
- 04Combination with NAD+ precursors (NMN, NR) is mechanistically promising but unstudied in any species at clinical scale.
- 05Synergy or interference with GLP-1 receptor agonists for combined fat-loss strategies is entirely speculative.
- 06Effects on related SAM-dependent methyltransferases — selectivity has been demonstrated in vitro, but in vivo selectivity over chronic human dosing is unknown.
Forms & Administration
5-Amino-1MQ is available as an oral capsule through some compounding pharmacies, typically at 50-150 mg daily. In mouse studies, it was administered via subcutaneous injection at 20 mg/kg three times daily. Optimal human dosing is not established. All medications should only be used under the guidance of a qualified healthcare provider.
Dosing & Protocols
The ranges below reflect protocols commonly discussed in the literature and by clinicians — not a prescription. Actual dosing for any individual should be determined by a qualified healthcare provider who knows the patient.
Typical Range
There is no clinically validated human dose because no human clinical trials have been conducted. Compounded oral capsules from US compounding pharmacies typically come in the 50–150 mg daily range, but these doses are extrapolated from mouse pharmacology rather than derived from any human dose-ranging study. The published mouse protocol used 20 mg/kg three times daily subcutaneously — an allometric scaling to humans is fraught and the oral-bioavailability question is itself unresolved.
Frequency
Compounded oral capsules are typically taken once daily, though some protocols split into twice-daily dosing on the assumption of shorter human half-life. The mouse studies dosed three times daily by injection. None of these regimens are evidence-based in humans.
Timing Considerations
No specific timing requirements: can be administered at any time of day, with or without food, and is not tied to exercise timing. Consistency matters more than the specific clock — dose at roughly the same time each day (or same day each week, for weekly protocols) to keep exposure steady.
Cycle Length
Some compounding pharmacy protocols recommend cycles of 8–12 weeks on, 2–4 weeks off, but this cycling pattern reflects general convention applied to longevity compounds rather than NNMT-specific evidence. Long-term safety of chronic NNMT inhibition in humans is unknown — NNMT has roles in cancer biology that warrant caution about indefinite use until those questions are addressed.
Protocol Notes
5-amino-1MQ occupies a particular position in the metabolic-optimization landscape: an unstudied small molecule with promising rodent data, available through legitimate compounding pharmacies with a prescription as well as through research-chemical suppliers, and discussed as a 'fat loss without appetite suppression' option that could complement GLP-1 therapy. The mechanistic premise is real and validated — NNMT's role in adipose metabolism is well-established — but the leap from 11 days of mouse dosing to chronic human use rests on essentially no data. Anyone using 5-amino-1MQ should understand that they are not taking a clinical drug and that the dosing, the safety profile, and the long-term oncological implications of chronic NNMT inhibition are all uncharacterized in humans.
5-amino-1MQ is not FDA-approved for any indication. No human clinical trials have been published. The doses cited reflect compounding-pharmacy convention extrapolated from rodent data, not validated human dosing.
Timeline of Effects
Onset
In the published mouse study, body weight differences from controls emerged within the 11-day dosing window. No human onset data exist. Compounding-pharmacy users typically report subjective changes in metabolic markers (energy, body composition shifts) over weeks to months, but these reports are anecdotal and not validated against placebo or against any objective measure.
Peak Effect
The published mouse data covered 11 days; longer-duration kinetics in any species are not well characterized. Whether the metabolic effects plateau, continue to accumulate, or attenuate with chronic dosing is unknown.
After Discontinuation
No formal washout data exist in mice or humans. Mechanistically, NNMT inhibition would be expected to reverse within days of stopping the compound as enzyme activity returns to baseline; whether the metabolic and body-composition effects persist or revert is undetermined. Anecdotal reports suggest gradual reversion of subjective metabolic effects after cessation, but objective data are absent.
Common Questions
Who 5-Amino-1MQ Is NOT For
- •Pregnancy and breastfeeding — no human safety data; NNMT plays roles in epigenetic regulation that warrant strong caution during fetal and infant development.
- •Active or recent-history cancer — NNMT has been characterized as both tumor-promoting and tumor-suppressing depending on cancer type and context. The lack of long-term oncological data in humans makes chronic NNMT inhibition unwise in patients with active malignancy or recent cancer history until those questions are resolved.
- •Pediatric use — entirely unstudied; no plausible justification for use in a developing population.
- •Significant hepatic impairment — first-pass metabolism, drug clearance, and the consequences of NAD+/SAM modulation in compromised liver tissue are uncharacterized.
- •Concurrent use of methotrexate or other antifolate therapies — theoretical interaction via SAM and one-carbon metabolism perturbation, though magnitude in humans is unknown.
- •Known hypersensitivity to quinolinium compounds or to compounding excipients.
Drug & Supplement Interactions
Documented drug-interaction data for 5-amino-1MQ in humans are essentially absent because no human clinical trials have been performed. Theoretical interactions follow from the mechanism (NNMT inhibition raises intracellular NAD+ and SAM, modulates polyamine metabolism, and alters one-carbon flux). Co-administration with NAD+ precursors (NMN, NR) is mechanistically synergistic — increasing NAD+ supply while blocking its degradation — and is the most commonly discussed combination in the longevity space, though no human data evaluate the safety or magnitude of any synergy. Co-administration with methotrexate or other antifolates could theoretically interact through perturbation of one-carbon metabolism and SAM levels, but the clinical relevance has not been characterized. Effects on drug-metabolizing enzymes (CYPs) have not been systematically studied. Co-administration with other off-label longevity compounds (rapamycin, metformin, GLP-1 agonists) is widely discussed but entirely unstudied. Anyone combining 5-amino-1MQ with chronic medications should disclose use to their prescribing clinician, recognizing that absence of documented interactions reflects absence of study, not safety.
Safety Profile
Common Side Effects
Cautions
- • No human clinical trials have been conducted
- • Not FDA-approved
- • NNMT plays roles beyond fat metabolism (epigenetics, cancer biology) — chronic inhibition effects unknown
- • Highly selective for NNMT (does not inhibit related SAM-dependent methyltransferases), which is favorable for safety
What We Don't Know
Human pharmacokinetics, dosing, and safety are entirely unknown. NNMT has roles in cancer biology (both tumor-promoting and tumor-suppressing depending on context) — whether long-term NNMT inhibition has oncological implications is unstudied. The 11-day mouse study is too short to assess chronic safety.
Legal Status
United States
5-amino-1MQ is not FDA-approved for any indication. It is available through some US compounding pharmacies with a prescription, where the regulatory basis is contested under FDA 503A rules (the bulk drug substance is not on the FDA approved list). Research-chemical suppliers sell 5-amino-1MQ for laboratory research use only; this material is not authorized for human use, and quality and purity vary widely.
International
No regulatory authority in any major jurisdiction has approved 5-amino-1MQ. Availability outside the US is primarily through grey-market and research-chemical channels.
Sports & Competition
5-amino-1MQ is not currently listed by name on the WADA Prohibited List, but it falls under WADA's S0 category (substances not approved by any government regulatory health authority for human therapeutic use). Athletes subject to WADA, USADA, or equivalent codes should treat it as prohibited in and out of competition.
Regulatory status changes over time. Verify current local rules with a qualified professional.
Myths & Misconceptions
Myth
5-amino-1MQ is a peptide.
Reality
5-amino-1MQ is a small-molecule quinolinium derivative, not a peptide. It is included on this site because it is widely discussed alongside metabolic peptides in the longevity and optimization community, but the molecule, mechanism, and class are entirely distinct from peptide hormone analogs.
Myth
Because 5-amino-1MQ doesn't suppress appetite, it has no side effects.
Reality
The absence of appetite effects is a mechanistic feature, not a safety claim. The actual safety profile in humans is uncharacterized because no human clinical trials have been performed. The mouse studies were 11 days long, which is far too short to assess chronic safety in any species, and tells us nothing about long-term oncological, hepatic, or metabolic consequences of NNMT inhibition.
Myth
5-amino-1MQ is FDA-approved for weight loss because it's available through compounding pharmacies.
Reality
5-amino-1MQ is not FDA-approved for any indication. Its availability through some US compounding pharmacies rests on a contested regulatory basis under FDA 503A rules; the active ingredient is not on the FDA approved bulk drug substances list. Compounded availability is not the same as FDA approval.
Myth
Combining 5-amino-1MQ with NMN or NR is proven synergistic for longevity.
Reality
The combination is mechanistically rational — NMN/NR raise NAD+ supply, 5-amino-1MQ blocks its degradation — but the synergy is theoretical. No published human studies evaluate the combination, and no clinical outcome data support the longevity claim. Mechanistic plausibility is not the same as clinical evidence.
Published Research
5 studiesExploring NNMT: from metabolic pathways to therapeutic targets.
Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity.
Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.
The Neelakantan et al. foundational paper — demonstrated that 11 days of 5-amino-1MQ in diet-induced obese mice produced 5.1% weight loss and 35% reduction in white adipose tissue without altering food intake. The anchor preclinical study driving 5-amino-1MQ's metabolic positioning.
Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice.
Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes.
Popular Stacks Including 5-Amino-1MQ
Quick Facts
- Class
- Metabolic Modulator
- Tier
- D
- Evidence
- Preliminary
- Safety
- Limited Data
- Updated
- Apr 2026
- Citations
- 5PubMed
Also known as
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Evidence Score
Clinical Trials
View Clinical TrialsLinks to ClinicalTrials.gov for reference. Listing does not imply endorsement.