5-Amino-1MQ

Mechanism of Action

5-Amino-1MQ functions by inhibiting NNMT, an enzyme that methylates nicotinamide and thereby reduces available NAD+ pools. By blocking NNMT activity, the compound has been shown in preclinical models to increase intracellular NAD+ concentrations, upregulate sirtuin-mediated metabolic pathways, and promote energy expenditure. In diet-induced obese (DIO) mouse models, this mechanism has been associated with reduced fat mass without changes in food intake, suggesting a direct effect on adipocyte metabolism rather than satiety signaling pathways.

Research Applications

• Studies have investigated its effects on adipose tissue metabolism in DIO mouse models
• Research has examined its role in NAD+ metabolism and sirtuin pathway activation
• Preclinical work has explored NNMT inhibition as a target for metabolic pathway research
• Studies have assessed its effects on cholesterol and lipid profiles in animal models

Key Published Studies

1. Neelakantan H, et al. 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.

   Key finding: Research investigated NNMT inhibitor-mediated effects on adipose tissue metabolism in DIO mice, observing changes in body composition and adipose tissue mass over 11 days without alterations in food intake behavior.

2. Neelakantan H, et al. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem. 2017;60(12):5015-5028.

   Key finding: Established the SAR for NNMT inhibitors and identified 5-Amino-1MQ as a potent, cell-permeable inhibitor with favorable pharmacological properties.

Chemical Properties

Type

Small Molecule

Molecular Formula

C₁₁H₁₂N₂O

Molar Mass

188.23 g/mol