5-Amino-1MQ (with NADH)

A Comprehensive Research Review of NNMT Inhibition Combined with NAD+ Cofactor Support

Introduction and Overview

The 5-Amino-1MQ with NADH blend represents a dual-compound research formulation that targets two convergent aspects of cellular nicotinamide adenine dinucleotide (NAD+) biology. The first component, 5-Amino-1MQ (5-amino-1-methylquinolinium), is a synthetic smallmolecule inhibitor of the cytosolic enzyme nicotinamide N-methyltransferase (NNMT). The second component, NADH (reduced nicotinamide adenine dinucleotide), is the biologically active reduced form of the NAD+ coenzyme that participates directly in mitochondrial electron transport and cellular redox reactions. The rationale for combining these two compounds is rooted in complementary mechanisms of action within NAD+ metabolism. NNMT is an enzyme that consumes nicotinamide—the primary substrate for NAD+ salvage synthesis—by methylating it into 1-methylnicotinamide (1MNA), a metabolic dead end that cannot be recycled back into the NAD+ pool. By inhibiting NNMT, 5-Amino-1MQ preserves nicotinamide within the salvage pathway, theoretically increasing the substrate available for NAD+ biosynthesis. NADH, in turn, serves as the reduced electron carrier that feeds directly into Complex I of the mitochondrial electron transport chain, driving oxidative phosphorylation and ATP generation. Researchers have described this dual approach as simultaneously “plugging the drain” on NAD+ consumption (via NNMT inhibition) while “filling the pool” with the bioactive reduced cofactor (via exogenous NADH). The combination has attracted interest in metabolic research, particularly in experimental models investigating cellular bioenergetics, adipocyte metabolism, skeletal muscle physiology, and age-related changes in NAD+ homeostasis. 5-Amino-1MQ was first characterized in 2017 by Neelakantan and colleagues at the University of Texas Medical Branch during a structure-activity relationship study screening quinolinium compounds for NNMT inhibitory potency and membrane permeability. NADH has been studied since the mid-20th century as a fundamental coenzyme in cellular metabolism, with its role in the electron transport chain first demonstrated by Friedkin and Lehninger in 1949. The combination of these two compounds into a single research formulation is a more recent development in the peptide and metabolic research supply landscape. This article reviews the available preclinical and in vitro literature on both 5-Amino-1MQ and NADH, examines their individual and combined mechanisms of action, summarizes key research findings, and provides practical information on reconstitution, storage, and handling for laboratory use. All information presented is based on published research and is intended for educational purposes only. This article does not constitute medical advice, and all compounds discussed are intended exclusively for in vitro laboratory research.

How It Works

5-Amino-1MQ: NNMT Inhibition and the NAD+ Salvage Pathway

5-Amino-1MQ (molecular formula C₁₀H₁₁N₂⁺, molecular weight 159.21 g/mol for the free base) is a quaternary ammonium small molecule—not a peptide—that acts as a selective, competitive inhibitor of nicotinamide N-methyltransferase (NNMT). It belongs to the methylquinolinium family of compounds and was selected for its combination of potent NNMT inhibition and high membrane permeability, properties that earlier NNMT inhibitors lacked.

NNMT is a cytosolic enzyme that catalyzes the transfer of a methyl group from Sadenosylmethionine (SAM) to nicotinamide (NAM), producing 1-methylnicotinamide (1-MNA) and S-adenosylhomocysteine (SAH). This reaction has two significant metabolic consequences. First, the nicotinamide that NNMT consumes is the primary substrate for the NAD+ salvage pathway—the dominant route through which mammalian cells regenerate NAD+. By diverting nicotinamide away from salvage, elevated NNMT activity reduces the cellular pool of NAD+ available for redox reactions, sirtuin activity, and DNA repair enzymes such as PARPs. Second, each NNMT reaction consumes one molecule of SAM, the universal methyl donor required for histone methylation, DNA methylation, polyamine synthesis, and numerous other critical methylation reactions.

5-Amino-1MQ inhibits NNMT with an IC₅₀ of approximately 1 µM in biochemical assays. In differentiated adipocyte cell models, the effective concentration for reducing intracellular 1MNA (EC₅₀) has been reported at 2.3 ± 1.1 µM. When NNMT is inhibited, several measurable shifts occur in vitro: intracellular NAD+ levels increase as more nicotinamide feeds the salvage pathway; SAM levels increase as less SAM is consumed by NNMT reactions; histone H3K4 methylation increases with greater SAM availability; and 1-MNA levels decline, confirming ontarget enzyme engagement.

Importantly, 5-Amino-1MQ exhibits high selectivity for NNMT and does not significantly inhibit related SAM-dependent methyltransferases or enzymes within the NAD+ salvage pathway itself, including NAMPT (nicotinamide phosphoribosyltransferase), the rate-limiting enzyme in salvage synthesis. This selectivity has been confirmed in enzymatic selectivity panels published alongside the original characterization studies.

NADH: The Reduced Cofactor in Mitochondrial Electron Transport

NADH (reduced nicotinamide adenine dinucleotide, molecular formula C₂₁H₂₉N₇O₁₄P₂, molecular weight 665.44 g/mol) is the reduced form of NAD+. In cellular metabolism, NAD+ accepts electrons during catabolic reactions—glycolysis, the tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation—to become NADH. This NADH then donates its electrons to Complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial electron transport chain, driving the proton gradient that powers ATP synthase and generates the majority of cellular ATP through oxidative phosphorylation. The NAD+/NADH ratio is a critical indicator of cellular redox state and metabolic health. In healthy mammalian tissues, the cytosolic NAD+/NADH ratio is estimated at approximately 700:1, strongly favoring the oxidized form to support catabolic reactions. Mitochondrial NAD+ constitutes 40–70% of total cellular NAD+, and the mitochondrial NAD+/NADH ratio is maintained at different levels to support the electron transport chain. Disruption of this ratio— whether by declining total NAD+ levels, impaired Complex I activity, or altered redox balance— has been associated with mitochondrial dysfunction in various experimental models. Exogenous NADH supplementation provides the reduced cofactor directly, bypassing the need for endogenous reduction of NAD+ through catabolic pathways. In research contexts, NADH has been studied for its potential to support mitochondrial electron transport, ATP generation, and cellular redox homeostasis, particularly in models where NAD+ metabolism is compromised or where mitochondrial function is being experimentally evaluated.

Rationale for the Combination

The mechanistic rationale for combining 5-Amino-1MQ with NADH centers on addressing NAD+ biology from two directions simultaneously. 5-Amino-1MQ acts upstream by preserving nicotinamide within the salvage pathway, preventing its wasteful methylation by NNMT. NADH acts downstream by providing the reduced electron carrier that directly participates in mitochondrial ATP production. This dual approach has been described in the research literature as combining a “conservation” strategy (preventing NAD+ precursor loss) with a “supply” strategy (providing the active cofactor directly). Additionally, because NNMT inhibition also conserves SAM, the combination may have implications for methylation-dependent epigenetic processes. Increased SAM availability could influence histone and DNA methylation patterns, potentially shifting gene expression profiles in metabolically relevant directions. However, these epigenetic effects remain an active area of investigation and are not yet well characterized in the context of combined 5-Amino1MQ/NADH formulations.

Research Benefits

NAD+ Metabolism and Cellular Bioenergetics

The primary area of research interest for this blend involves NAD+ metabolism. NNMT inhibition by 5-Amino-1MQ has been shown to increase intracellular NAD+ levels in adipocyte cell models by preserving the nicotinamide substrate pool. Combined with exogenous NADH, which serves as a direct electron donor for oxidative phosphorylation, the blend targets both the biosynthesis and utilization arms of NAD+ biology. Researchers studying cellular bioenergetics, mitochondrial function, and redox homeostasis have utilized these compounds individually and in combination to probe how NAD+ availability influences metabolic outputs such as ATP production, oxygen consumption rate, and mitochondrial membrane potential.

Adipocyte Metabolism and Lipid Research

NNMT is highly expressed in white adipose tissue, and its expression levels are significantly elevated in adipose tissue from obese animal models compared to lean controls. In vitro studies using differentiated 3T3-L1 adipocytes have demonstrated that 5-Amino-1MQ treatment at 30

µM concentration significantly reduces intracellular 1-MNA levels, increases intracellular NAD+, and suppresses lipogenesis. In vivo studies in diet-induced obese (DIO) mouse models have reported that 5-Amino-1MQ treatment (20 mg/kg three times daily via subcutaneous injection for 11 days) resulted in significant reductions in body weight, white adipose tissue mass, and adipocyte size without affecting food intake or producing observable adverse effects. These findings have positioned NNMT as a target of active investigation in metabolic research.

Skeletal Muscle Physiology

A 2024 study published in Scientific Reports by Dimet-Wiley and colleagues at the University of Texas Medical Branch evaluated the effects of 5-Amino-1MQ on skeletal muscle function in aged mice. The study found that 5-Amino-1MQ treatment improved grip strength to a greater degree than rigorous exercise training alone. When combined with progressive weighted exercise, 5-Amino-1MQ-treated mice exhibited approximately 150% increases in daily running distance that were more sustained compared to exercise-only controls, which showed initial increases that tapered significantly by weeks 7 and 8. The researchers also reported that 5Amino-1MQ treatment and exercise training independently reduced muscle cell fat content in the gastrocnemius muscle.

Muscle Stem Cell Research

NNMT inhibition has been investigated in the context of muscle satellite cell (MuSC) biology. Age-associated changes in MuSC responsiveness and regenerative capacity are key areas of sarcopenia research. Preclinical studies have reported that NNMT inhibition is associated with increased activity of aged MuSC populations and shifts in muscle tissue repair metrics in animal models. In one study, NNMT inhibitor-treated mice experienced a two-fold increase in myofiber cross-sectional area and 70% stronger contractile force in healed tissue compared to untreated controls.

Mitochondrial Electron Transport Research

NADH serves as the primary electron donor to Complex I of the mitochondrial electron transport chain. Research into mitochondrial function has demonstrated that the NAD+/NADH ratio directly influences the rate of oxidative phosphorylation, ATP production, and reactive oxygen

species (ROS) generation. Studies using mitochondrial DNA depletion models have shown that maintenance of NADH oxidation is sufficient to preserve histone acetylation patterns and prevent DNA methylation changes that result from mitochondrial dysfunction, independent of mitochondrial ATP production. These findings underscore the importance of NADH availability in maintaining both metabolic and epigenetic homeostasis.

What the Science Shows

Neelakantan et al. (2017) — Journal of Medicinal Chemistry

This foundational study characterized 5-Amino-1MQ as a potent, selective, membranepermeable NNMT inhibitor. The researchers screened a series of 1-methylquinolinium compounds with various amine substitutions, evaluating NNMT inhibitory potency, passive membrane permeability (PAMPA assay), and active transport (Caco-2 bidirectional permeability assay). 5-Amino-1MQ emerged as the lead compound due to its combination of high NNMT inhibition, high membrane permeability, and low cytotoxicity. Treatment of 3T3-L1 adipocytes with 10 µM 5-Amino-1MQ for 24 hours did not impact cell viability. The study confirmed that 5-Amino-1MQ significantly reduced intracellular 1-MNA and increased intracellular NAD+ in differentiated adipocytes.

Neelakantan et al. (2018) — Biochemical Pharmacology

This follow-up study evaluated 5-Amino-1MQ in a diet-induced obesity (DIO) mouse model. After 16 weeks on a high-fat diet, obese mice were treated with 5-Amino-1MQ at 20 mg/kg three times daily via subcutaneous injection for 11 days. The treatment group showed significant reductions in body weight, white adipose tissue mass, and adipocyte size compared to vehicletreated controls. Notably, food intake was not significantly different between treatment and control groups, suggesting the observed effects were not mediated by appetite suppression. No observable adverse effects were reported during the treatment period.

Dimet-Wiley et al. (2024) — Scientific Reports

This study examined the effects of NNMT inhibition on skeletal muscle function in aged mice. Using a progressive weighted wheel running (PoWeR) model, the researchers compared exercise alone, 5-Amino-1MQ alone, and the combination. The 5-Amino-1MQ-treated exercise group showed approximately 150% sustained increases in daily running distance compared to approximately 75% for the exercise-only group, which tapered off at weeks 7 and 8. Grip strength improvements were greater with 5-Amino-1MQ treatment than with exercise alone. Both 5-Amino-1MQ and exercise independently reduced intramyocellular lipid content in oxidative and glycolytic muscle fibers. The researchers concluded that the additive effects of 5Amino-1MQ suggest the compound influences molecular pathways differently from exercise training.

NAD+ Metabolism and Mitochondrial Function – Multiple Studies

The role of NADH in mitochondrial electron transport has been established through decades of biochemistry research. Friedkin and Lehninger (1949) first demonstrated that NADH links metabolic pathways such as the TCA cycle with ATP synthesis through oxidative phosphorylation. More recent work has characterized the compartmentalization of NAD+/NADH pools between the cytosol and mitochondria, with mitochondrial NAD+ constituting 40–70% of the total cellular pool. Research by Cambronne et al. (2016) and subsequent studies have developed genetic tools for measuring NAD+/NADH dynamics in living cells, enabling more precise characterization of how perturbations to NAD+ metabolism influence mitochondrial function, redox balance, and epigenetic regulation.

Dosing Protocol

The following dosing information is derived from published preclinical research studies and is provided for reference purposes only. No human clinical trials have been conducted with 5Amino-1MQ, and this compound has not been approved for human use by the FDA or any other regulatory authority. All dosing information pertains to experimental models.

5-Amino-1MQ Dosing in Preclinical Studies

• DIO Mouse Model (Neelakantan et al., 2018): 20 mg/kg per injection, three times daily via subcutaneous injection, for a total daily dose of approximately 34 mg/kg (calculated by free weight of the parent compound). Treatment duration: 11 days.
• Aged Mouse Muscle Study (Dimet-Wiley et al., 2024): Administered alongside progressive weighted exercise training over an 8-week period. Specific dosing protocols were consistent with prior published NNMT inhibitor studies from the same research group.
• In Vitro Adipocyte Studies: 10–30 µM concentrations used in differentiated 3T3-L1 adipocyte assays. Treatment durations of 24 hours for mechanistic endpoint measurements.

Blend Uses

Pre-Workout Boost: This blend can be utilized as a pre-workout blend administered 30-45 minutes before a training session. It may be especially beneficial before fasted cardio to burn stubborn belly fat more efficiently. General Fat Loss and Mitochondrial Health: This blend could be administered daily, every other day, or 5 on/2 off.

Common Dosage Ranges: Method of administration: Subcutaneous or intramuscular. Dosage: 5mg-50mg Frequency: Administered on training days or as needed anywhere from 3-5x per week.

Side Effects

Preclinical Safety Profile of 5-Amino-1MQ In published preclinical studies, 5-Amino-1MQ has demonstrated a favorable safety profile. In the 2018 DIO mouse study by Neelakantan and colleagues, 11 days of subcutaneous administration at 20 mg/kg three times daily produced no observable adverse effects. In vitro cytotoxicity testing in 3T3-L1 preadipocytes showed no impact on cell viability at concentrations up to 10 µM over 24 hours of exposure. Food intake was not significantly altered in treated animals, suggesting the compound does not produce anorexic effects at the doses studied.

NADH Safety Considerations

NADH is an endogenous coenzyme present in all living cells and has a well-established biochemical profile. In research settings, NADH is handled as a standard laboratory reagent. The compound is sensitive to light, heat, and oxidation, and degradation products should be

considered when interpreting experimental results. NADH does not present unusual toxicity concerns in standard in vitro experimental concentrations.

Limitations of Current Safety Data

It is important to emphasize that no human clinical trials have been conducted with 5-Amino1MQ. All safety data derives from in vitro cell assays and short-term animal studies. Long-term effects, potential drug interactions, reproductive toxicity, genotoxicity, and carcinogenicity have not been evaluated. The absence of adverse effects in short-term preclinical studies does not guarantee safety in other experimental systems or over extended exposure periods. Researchers should follow all institutional safety protocols when handling these compounds.

Contraindications and Precautions

As 5-Amino-1MQ has not been evaluated in human clinical trials, no formal contraindication profile has been established. In preclinical research contexts, the following considerations apply:

• 5-Amino-1MQ is classified as an experimental small-molecule compound and has not been approved for human or veterinary use by any regulatory authority.
• The compound is a known chemical irritant in its iodide salt form. Standard laboratory safety precautions should be observed, including the use of nitrile gloves, safety goggles, and appropriate personal protective equipment.
• NADH is light-sensitive and oxidation-prone. Experimental protocols should account for potential degradation when designing assays involving NADH-containing formulations.
• Researchers working with combined formulations should be aware that the interaction profile between NNMT inhibitors and exogenous NADH has not been extensively characterized in published literature.
• All handling should comply with institutional biosafety protocols and applicable regulations for research-use-only chemical compounds.

Comparison with Related Compounds

5-Amino-1MQ vs. NMN and NR (NAD+ Precursor Supplementation)

Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are NAD+ precursors that attempt to increase cellular NAD+ levels by providing additional substrate for the salvage pathway. 5-Amino-1MQ takes a fundamentally different approach: rather than adding more precursor material, it prevents the existing nicotinamide from being diverted away from salvage synthesis by NNMT. Researchers have described this distinction as “pouring more water into the bucket” (NMN/NR) versus “plugging the hole in the bucket” (NNMT inhibition). The two strategies are not mutually exclusive, and some 2024–2025 research protocols have investigated combined approaches.

5-Amino-1MQ vs. Other NNMT Inhibitors

JBSNF-000088 is another small-molecule NNMT inhibitor that has been studied in preclinical metabolic disease models. While both compounds target the same enzyme, 5-Amino-1MQ was the first to demonstrate both high NNMT potency and sufficient membrane permeability for intracellular activity in living cells. Earlier NNMT inhibitors, such as 1,2,4,8tetramethylquinolinium, showed potent enzymatic inhibition in cell-free assays but lacked the membrane permeability required for intracellular engagement. 5-Amino-1MQ remains the most widely cited pharmacological tool for studying NNMT function in adipocyte and muscle research.

NADH vs. NAD+ (Oxidized Form)

NAD+ and NADH represent the oxidized and reduced forms of the same coenzyme, and they serve different functions in cellular metabolism. NAD+ acts as an electron acceptor in catabolic reactions (glycolysis, TCA cycle, β-oxidation), while NADH acts as an electron donor to the mitochondrial electron transport chain. Exogenous NAD+ supplementation supports the oxidized pool needed for sirtuin activity, PARP-mediated DNA repair, and catabolic metabolism. Exogenous NADH supplementation supports the reduced pool needed for mitochondrial ATP production. The choice between NAD+ and NADH in research formulations depends on the specific metabolic endpoints being investigated.

Research Success Tips

• Reconstitute lyophilized material fresh before each experimental use period to minimize degradation, particularly of the NADH component, which is oxidation-sensitive.
• Store reconstituted solutions protected from light. NADH undergoes photodegradation, and uncontrolled light exposure can compromise experimental reproducibility.
• When designing in vitro assays, include appropriate vehicle controls and account for the potential independent effects of each component by including single-agent arms alongside the combination.
• For NNMT activity confirmation, measure intracellular 1-MNA levels by LC-MS/MS as a direct readout of on-target engagement, as described in the Neelakantan et al. (2017) methodology.
• Monitor the NAD+/NADH ratio rather than absolute levels of either species alone, as the ratio provides a more physiologically meaningful indicator of cellular redox state and metabolic health.
• Use analytical-grade compounds with certificates of analysis (COA) confirming identity and purity. HPLC purity verification and LC-MS molecular identity confirmation are recommended minimum quality standards.

Storage and Handling

• Lyophilized (Unreconstituted): Store at -20°C or below, sealed, protected from light and moisture. Under these conditions, lyophilized material is generally stable for 24 months or more.
• Reconstituted Solution: Store at 2–8°C (refrigerated), protected from light. Use within 14–28 days of reconstitution depending on the solvent used and storage conditions.
• Light Sensitivity: NADH is highly sensitive to photodegradation. All storage and handling should be performed with minimal light exposure. Amber vials or foil wrapping are recommended for reconstituted solutions.
• Freeze-Thaw Cycles: Minimize repeated freeze-thaw cycles, which can degrade both the small molecule and cofactor components. Aliquot reconstituted material into single-use portions if multiple experimental sessions are planned.
• Handling Precautions: Use standard laboratory PPE including nitrile gloves and safety goggles. The iodide salt form of 5-Amino-1MQ is a known irritant (H302: harmful if swallowed; H315: causes skin irritation; H319: causes serious eye irritation).

Legal Status

5-Amino-1MQ is classified as a research chemical and is not approved for human or veterinary use by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. It has not entered human clinical trials and has no established safety or efficacy profile in humans. The compound is available for purchase as a research-use-only (RUO) chemical for in vitro laboratory research and preclinical investigation. NADH is a naturally occurring coenzyme that is commercially available as both a research reagent and a dietary supplement. In its supplement form, NADH is marketed under various brand names and is not regulated as a drug. In the context of this research blend, NADH is supplied as a laboratory-grade reagent for in vitro research purposes. The sale and purchase of research-use-only compounds is subject to applicable federal, state, and local regulations. Buyers are responsible for ensuring compliance with all applicable laws governing the purchase, possession, and use of research chemicals in their jurisdiction. This compound is not intended for use in humans or animals and is not intended to diagnose, treat, cure, or prevent any disease.

Frequently Asked Questions

What is 5-Amino-1MQ?

5-Amino-1MQ is a synthetic small-molecule inhibitor of the enzyme nicotinamide Nmethyltransferase (NNMT). It is a quaternary ammonium compound belonging to the methylquinolinium family. It is not a peptide.

What is NADH?

NADH is the reduced form of nicotinamide adenine dinucleotide (NAD+), a coenzyme found in all living cells. NADH serves as the primary electron donor to Complex I of the mitochondrial electron transport chain, driving ATP production through oxidative phosphorylation.

Why are these two compounds combined?

The combination targets NAD+ biology from two directions: 5-Amino-1MQ preserves the nicotinamide substrate needed for NAD+ biosynthesis by inhibiting NNMT, while NADH provides the reduced cofactor that directly participates in mitochondrial energy production.

Has 5-Amino-1MQ been tested in humans?

No. As of the date of this publication, 5-Amino-1MQ has not entered human clinical trials. All available data derives from in vitro cell assays and preclinical animal studies. The compound has not been approved for human use by the FDA or any other regulatory authority.

Is 5-Amino-1MQ a peptide?

No. 5-Amino-1MQ is a small-molecule compound with a molecular weight of approximately 159 g/mol. It is a quaternary ammonium salt, not a peptide or protein.

How should this blend be stored?

Store lyophilized material at -20°C or below, sealed, and protected from light and moisture. After reconstitution, store at 2–8°C, protected from light, and use within the timeframe recommended for the specific solvent used.

What is NNMT and why does it matter for NAD+ levels?

NNMT (nicotinamide N-methyltransferase) is a cytosolic enzyme that methylates nicotinamide, converting it into 1-methylnicotinamide (1-MNA)—a dead-end metabolite that cannot be recycled back into NAD+. When NNMT activity is elevated, as observed in adipose tissue from obese animal models, more nicotinamide is diverted away from the NAD+ salvage pathway, reducing the pool of NAD+ available for cellular metabolism. Inhibiting NNMT preserves nicotinamide for NAD+ biosynthesis.

Can this blend be used alongside other NAD+ precursors such as NMN or NR in research?

In principle, NNMT inhibition (5-Amino-1MQ) and NAD+ precursor supplementation (NMN or NR) target different points in NAD+ metabolism and could be investigated in combination. Some recent research protocols have explored dual approaches. However, the interaction profile of these combined strategies is not yet well characterized in published literature, and researchers should design appropriate controls.

References

1. Neelakantan H, Wang HY, Lauderdale VP, Kishi T, Kamalakaran PA, Drove SA, Khaua RA, Thibodeaux SJ, Bhatt DP, Rojas A, Bianchi-Smiraglia A, Nikiforov MA, Nickels JT, Holbert CE, Casero RA, Bhatt AP, Watowich SJ. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141–152.

2. Neelakantan H, Brightwell CR, Graber TG, Maroto R, Wang HY, McHargue DT, Papaconstantinou J, Fry CS, Watowich SJ. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019;163:481–492.

3. Dimet-Wiley AL, Latham CM, Brightwell CR, Neelakantan H, Keeble AR, Thomas NT, Noehren B, Fry CS, Watowich SJ. Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Sci Rep. 2024;14(1):15554.

4. Neelakantan H, Vance V, Wetzel MD, Wang HY, McHargue DT, Otani H, Snezhkova LV, Bhatt DP, Kishi T, Nickels JT, Bhatt AP, Watowich SJ. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60(12):5015–5028.

5. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirber E, Sell H, Eckel J, Léonardson G, Bhatt DP, Nickels JT, Sr, Bhatt AP, Spiegelman BM. Nicotinamide Nmethyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258–262.

6. Friedkin M, Lehninger AL. Esterification of inorganic phosphate coupled to electron transport between dihydrodiphosphopyridine nucleotide and oxygen. J Biol Chem. 1949;178(2):611–623.

7. Cambronne XA, Stewart ML, Kim D, Jones-Brunette AM, Morgan RK, Farrens DL, Cohen MS, Bhatt DP, Goodman RH. Biosensor reveals multiple sources for mitochondrial NAD+. Science. 2016;352(6292):1474–1477.

8. Martínez-Reyes I, Diebold LP, Kong H, Schieber M, Huang H, Hensley CT, Mehta MM, Wang T, Santos JH, Woychik R, Dufour E, Spelbrink JN, Weinberg SE, Zhao Y, DeBerardinis RJ, Chandel NS. Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation. PLoS Biol. 2020;18(4):e3000629.

9. Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, Li C, Shen G, Zou B. NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1):227.

10. Li W, Gao M, Hu C, Chen X, Zhou Y. NADH and NADPH in Biological Processes. In: Pharmacology and Potential Implications of Nicotinamide Adenine Dinucleotide Precursors. Aging Dis. 2021;12(8):2098–2119.

11. Roberti A, Fernández-Pérez A, Sosa-Costa A, Cossío FP, Esteller M. NNMT blockade during the initial phases of adipogenesis inhibits preadipocyte differentiation into adipocytes. Nucleic Acids Res. 2023;51(9):4266–4283.

12. Song Q, Chen Y, Wang J, Hao L, Huang C, Griffiths A, Sun Z, Zhou Z, Song Z. Nicotinamide N-methyltransferase (NNMT) in hepatocytes modulates hepatic glucose and lipid metabolism. Hepatology. 2020;73(5):1971–1983.