Metabolic signalling

    5-Amino-1MQ vs MOTS-c: Research Comparison

    5-Amino-1MQ and MOTS-c are both studied in metabolism research, but they are different kinds of molecule. 5-Amino-1MQ is a small synthetic molecule that blocks the enzyme NNMT. MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, linked in cell and mouse studies to the energy-sensing enzyme AMPK.

    Side-by-side comparison

    Attribute5-Amino-1MQMOTS-c
    What it isSmall synthetic molecule, not a peptide16-amino-acid peptide encoded in mitochondrial DNA
    Main targetBlocks the enzyme NNMT (nicotinamide N-methyltransferase)Linked to activation of AMPK, an energy-sensing enzyme
    Main models studiedCultured mouse fat cells and miceCells and mice
    Human dataNo published human studiesObservational studies of natural MOTS-c levels; a modified version (CB4211) completed a phase 1 trial with no results posted
    Who publishes most of the workMostly one research groupMostly the discovering group

    Detailed analysis

    5-Amino-1MQ (5-amino-1-methylquinolinium) blocks NNMT, an enzyme that adds a methyl group to nicotinamide, a form of vitamin B3. In cultured mouse fat cells it lowered the enzyme's product and raised NAD+ and SAM levels, and it has been studied in mice fed a high-fat diet (Neelakantan et al., 2018). Nearly all published studies come from one research group, and there are no published human studies. MOTS-c was described in 2015 (Lee et al., 2015). In cell and mouse studies it inhibits the folate cycle, which leads to activation of AMPK, and under metabolic stress it moves into the cell nucleus and changes the activity of many genes. Published human work so far measures natural MOTS-c levels, for example in muscle and blood after exercise. A modified version, CB4211, completed a phase 1 trial in 2021 with no results posted. The two act at different points: 5-Amino-1MQ on an enzyme in the NAD+ and methyl-donor pathways, MOTS-c on AMPK signalling. Neither has published controlled human trial results.

    Key differences

    • ·5-Amino-1MQ is a small synthetic molecule; MOTS-c is a peptide encoded in mitochondrial DNA.
    • ·5-Amino-1MQ blocks the enzyme NNMT; MOTS-c is linked to activation of AMPK.
    • ·Neither has published controlled human trial results.

    Research summary

    Both compounds are at an early stage. 5-Amino-1MQ evidence comes from cultured cells and mice, mostly from one group (Neelakantan et al., 2018). MOTS-c evidence comes from cells and mice (Lee et al., 2015) plus observational human studies of natural MOTS-c levels. Supplied for laboratory research use only.

    Frequently asked questions