Ordering from the Americas?Switch to the US store
Account
Research library, mechanism

NAD+ metabolism and nicotinamide N-methyltransferase (NNMT)

NAD+ is a coenzyme for redox reactions and a cosubstrate for sirtuins, CD38 and PARPs. NNMT is an enzyme that methylates nicotinamide, a component of NAD+ metabolism. NAD+ and 5-amino-1MQ, an NNMT inhibitor scaffold, are both non-peptide research materials in the catalog.

Written by the Peptency editorial teamLast reviewed 9 studies checked in PubMed on 5 October 2026

Research-use information. This page summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

What does the literature say about NAD+?

Reviews describe NAD+ as a coenzyme for redox reactions and an essential cofactor for sirtuins, CD38 and poly(ADP-ribose) polymerases, and discuss NAD+ homeostasis and the link between energy metabolism, mitochondria and the nucleus.[4],[8],[5],[9]

What is NNMT?

NNMT is a cytosolic enzyme that methylates nicotinamide and is described as regulating methylation potential and the degradation of nicotinamide. Reviews connect it to metabolism and to epigenetic regulation.[2],[3]

What has been published on NNMT inhibitors?

Structure-activity work identified N-methylquinolinium scaffolds with low micromolar inhibition of NNMT, and membrane-permeable methylquinolinium inhibitors were tested in cells and in mice on a high-fat diet. A 2026 review covers the obstacles to clinical translation.[7],[6],[1]

Which compounds in the catalog belong to this group?

Dinucleotide coenzyme (not a peptide)NAD+

C21H27N7O14P2, 663.4 g/mol

Small molecule, methylquinolinium (not a peptide)5-Amino-1MQ

C10H11N2+, 159.21 g/mol

Research materials: NAD+, 5-Amino-1MQ.

Which studies are cited on this page?

  1. [1] Puleo N, Allega MF, Niemann CU, Lengyel E. Emerging opportunities for nicotinamide N-methyltransferase (NNMT) inhibitor clinical translation. Trends Pharmacol Sci. 2026;47:638-654.

    Review of opportunities and obstacles for clinical translation of NNMT inhibitors.

    ReviewPMID 42067476DOI 10.1016/j.tips.2026.04.002

  2. [2] Iyamu ID, Huang R. Mechanisms and inhibitors of nicotinamide N-methyltransferase. RSC Med Chem. 2021;12:1254-1261.

    Review of NNMT mechanisms and inhibitor development.

    ReviewPMID 34458733DOI 10.1039/d1md00016k

  3. [3] Roberti A, Fernández AF, Fraga MF. Nicotinamide N-methyltransferase: At the crossroads between cellular metabolism and epigenetic regulation. Mol Metab. 2021;45:101165.

    Review of NNMT at the crossroads of cellular metabolism and epigenetic regulation.

    ReviewPMID 33453420DOI 10.1016/j.molmet.2021.101165

  4. [4] Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD+ metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22:119-141.

    Review of NAD+ metabolism and the roles of NAD+-dependent enzymes (sirtuins, CD38, PARPs) in cellular processes during ageing.

    ReviewPMID 33353981DOI 10.1038/s41580-020-00313-x

  5. [5] Katsyuba E, Romani M, Hofer D, Auwerx J. NAD+ homeostasis in health and disease. Nat Metab. 2020;2:9-31.

    Review of NAD+ homeostasis, biosynthesis pathways and sirtuin signalling.

    ReviewPMID 32694684DOI 10.1038/s42255-019-0161-5

  6. [6] Neelakantan H, Vance V, Wetzel MD, Wang HL, McHardy SF, Finnerty CC, 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.

    Tested membrane-permeable methylquinolinium NNMT inhibitors in cell culture and in diet-induced obese mice.

    In vitro and animal studyPMID 29155147DOI 10.1016/j.bcp.2017.11.007

  7. [7] Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem. 2017;60:5015-5028.

    Structure-activity relationships of small-molecule NNMT inhibitors, identifying N-methylquinolinium scaffolds with low micromolar inhibition (the scaffold class of 5-amino-1MQ).

    Chemistry and in vitro studyPMID 28548833DOI 10.1021/acs.jmedchem.7b00389

  8. [8] Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350:1208-13.

    Review of NAD+ as a coenzyme and as a cosubstrate for sirtuins and PARPs.

    ReviewPMID 26785480DOI 10.1126/science.aac4854

  9. [9] Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22:31-53.

    Review of NAD+ metabolism linking energy homeostasis, mitochondria and the nucleus.

    ReviewPMID 26118927DOI 10.1016/j.cmet.2015.05.023

Data dates: citations read from PubMed 2026-10-05.