MOTS-c / 5-Amino-1MQ

Quick answers

Molecular Profile

Type

Peptide / small-molecule blend

Components

Mechanism & Target Class

Combines a mitochondrial-derived peptide (MOTS-c) with a small-molecule enzyme inhibitor (5-Amino-1MQ) that act on separate metabolic pathways; no single target applies. MOTS-c is a short cationic peptide encoded by an open reading frame within mitochondrial 12S rRNA (MT-RNR1 locus); mechanistic studies link it to inhibition of the folate-methionine one-carbon cycle, AICAR accumulation, and AMP-activated protein kinase (AMPK) activation, with stress-responsive nuclear translocation. 5-Amino-1MQ is a substrate-site small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT; EC 2.1.1.1), the cytosolic enzyme that transfers a methyl group from S-adenosyl-L-methionine (SAM) to nicotinamide, yielding 1-methylnicotinamide (1-MNA) and S-adenosyl-L-homocysteine; the cationic quinolinium ring occupies the nicotinamide substrate-binding pocket.

Storage & Handling

Lyophilized

-20°C; components typically stable ~24 months desiccated and protected from light.

Handling

Avoid freeze-thaw; protect from light and moisture. The peptide component carries oxidation-sensitive methionine residues; the small-molecule salt is hygroscopic — keep desiccated.

References (23)

1. Reviews

   1

   Wan W, et al. (2023). J Transl Med

   DOI: 10.1186/s12967-023-03885-2

2. 2

   Yoon TK, et al. (2022). Diabetes Metab J

   DOI: 10.4093/dmj.2022.0092PubMed 35878432

3. 3

   Miller B, et al. (2022). J Clin Invest

   DOI: 10.1172/JCI158449PubMed 35320685

4. 4

   Frontiers in Pharmacology (2024 review) (2024). Frontiers in Pharmacology

   DOI: 10.3389/fphar.2024.1410479

5. 5

   Roberti A, Fernández AF, Fraga MF. (2021). Mol Metab

   DOI: 10.1016/j.molmet.2021.101165PubMed 33453420

6. 6

   Pissios P. (2017). Trends in Endocrinology & Metabolism

   DOI: 10.1016/j.tem.2017.02.004

7. Clinical

   7

   Reynolds JC, et al. (2021). Sci Rep

   DOI: 10.1038/s41598-021-96419-zNCT01140282

8. 8

   Qin Q, et al. (2018). Int J Cardiol

   DOI: 10.1016/j.ijcard.2017.11.002PubMed 29242099

9. Primary research

   9

   Kim SJ, et al. (2024). iScience

   PubMed 39559755

10. 10

    Kumagai H, et al. (2021). Am J Physiol Endocrinol Metab

    DOI: 10.1152/ajpendo.00275.2020PubMed 33554779

11. 11

    Reynolds JC, et al. (2021). Nat Commun

    DOI: 10.1038/s41467-020-20790-0PubMed 33473109

12. 12

    D'Souza RF, et al. (2020). Aging (Albany NY)

    DOI: 10.18632/aging.102944PubMed 32182209

13. 13

    Lu H, et al. (2019). J Mol Med

    DOI: 10.1007/s00109-018-01738-wPubMed 30725119

14. 14

    Kim KH, et al. (2018). Cell Metabolism

    DOI: 10.1016/j.cmet.2018.06.008PubMed 29972790

15. 15

    Lee C, et al. (2015). Cell Metabolism

    DOI: 10.1016/j.cmet.2015.02.009PubMed 25738459

16. 16

    Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H. (2024). Diabetes, Obesity and Metabolism

    DOI: 10.1111/dom.15879PubMed 39161060

17. 17

    Dimet-Wiley AL, et al. (2024). Scientific Reports

    DOI: 10.1038/s41598-024-66034-9

18. 18

    Awosemo O, Neelakantan H, Watowich S, Ma J, Wu L, Chow DS, Liang D. (2021). Journal of Pharmaceutical and Biomedical Analysis

    DOI: 10.1016/j.jpba.2021.114255PubMed 35192477

19. 19

    Sampson CM, Dimet AL, Neelakantan H, Ogunseye KO, Stevenson HL, Hommel JD, Watowich SJ. (2021). Scientific Reports

    DOI: 10.1038/s41598-021-85051-6PubMed 33707534

20. 20

    Neelakantan H, Brightwell CR, Graber TG, Maroto R, Wang HYL, McHardy SF, Papaconstantinou J, Fry CS, Watowich SJ. (2019). Biochemical Pharmacology

    DOI: 10.1016/j.bcp.2019.02.008PubMed 30753815

21. 21

    Neelakantan H, et al. (2018). Biochemical Pharmacology

    DOI: 10.1016/j.bcp.2017.11.007PubMed 29155147

22. 22

    Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. (2017). Journal of Medicinal Chemistry

    DOI: 10.1021/acs.jmedchem.7b00389PubMed 28548833

23. 23

    Kraus D, Yang Q, Kong D, et al. (2014). Nature

    DOI: 10.1038/nature13198PubMed 24717514

Related compounds

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• MOTS-c