Background and Mechanism

NNMT regulates methylation of nicotinamide, influencing intracellular pools of NAD+, a central cofactor in metabolic pathways. By attenuating NNMT activity, 5‑Amino‑1MQ has been observed in preclinical settings to elevate NAD+ availability, enhance metabolic flux, and upregulate downstream signaling programs associated with cellular stress responses and energy expenditure (e.g., SIRT1). In adipose models, reduced NNMT activity has been linked with smaller adipocyte size and diminished fat depots, suggesting a potential role for this inhibitor in fat mass modulation under research conditions.

Chemical Characteristics

CAS #: 42464-96-0
Molecular Formula: C₁₀H₁₁N₂
Molecular Weight: 159.21 g/mol

Research Highlights

1. Metabolic and Adiposity Findings (Preclinical)

– In murine research, short-term administration of 5‑Amino‑1MQ has been associated with measurable body‑mass reductions without corresponding decreases in food intake. Reports also describe shrinkage of adipocyte size and reductions in fat-pad mass while preserving insulin signaling markers in certain models.
– Mechanistically, these changes appear to coincide with elevated NAD+ and activation of metabolic gene programs consistent with increased energy expenditure.

2. Enzymatic Target: NNMT

– NNMT is highly expressed in adipose tissue and plays a role in cellular methyl‑donor economy and nicotinamide processing. Inhibition by 5‑Amino‑1MQ has been used in research to probe links between methylation status, redox state, and lipid metabolism.
– Downstream observations in models include transcriptional changes consistent with enhanced mitochondrial function and lipid utilization.

3. Form and Laboratory Handling Notes

– This document pertains to lyophilized powder supplied for laboratory applications. Reconstitution, aliquoting, and storage parameters should follow institutional SOPs and validated protocols for small‑molecule handling.
– For consistency across studies, document solvent, concentration, storage temperature, freeze–thaw cycles, and light exposure conditions in experimental records.

General Specifications (Research Grade)

Presentation: Lyophilized powder (research use)
Target: Nicotinamide N‑methyltransferase (NNMT) inhibitor
Suggested Use: In vitro / preclinical workflows as defined by protocol
Storage: Follow validated lab SOPs for small‑molecule lyophilizates

References

1. Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258–262. doi:10.1038/nature13198.

2. Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nature Chemical Biology. 2013;9:300–306. doi:10.1038/nchembio.1204.

3. Kannt A, Rajagopal S, Kadnur SV, Suresh J, Bhamidipati RK, Swaminathan S, Hallur MS, Kristam R, Pieper MP. Novel small molecule inhibitors of nicotinamide N-methyltransferase (NNMT). Bioorganic & Medicinal Chemistry Letters. 2018;28(17): 3071–3075. doi:10.1016/j.bmcl.2018.07.009. PMC5826726.

4. van der Vaart A, et al. Reduced calorie diet combined with NNMT inhibition establishes a metabolic memory. Scientific Reports. 2021;11:24840. doi:10.1038/s41598-021-03670-5.

5. Liu H, Liu D, Zhao X, Wright M, Guo H, Deng Y, Guo H. Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes. International Journal of Molecular Sciences. 2021;22(15): 8199. doi:10.3390/ijms22158199. PMC8337113.

6. Alston CL, et al. Nicotinamide N-methyltransferase: a novel therapeutic target. Drug Discovery Today. 2021;26(12): 2767–2778. doi:10.1016/j.drudis.2021.07.009.

7. Frontiers in Pharmacology. NNMT inhibition and metabolic regulation. 2024. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1410479/full

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