Therapeutic Targets of the NAD+ Biosynthesis Pathway

Therapeutic Targets of the NAD+ Biosynthesis Pathway

Nicotinamide adenine dinucleotide (NAD+), along with nicotinamide adenine dinucleotide phosphate (NADP+), are crucial cofactors found in cells. NADH represents the reduced form of NAD+, while NAD+ represents the oxidised form of NADH. Research has shown that NAD+ metabolism plays a significant role in regulating important biological effects, including lifespan. Through the action of poly-ADP-ribosyl polymerase (PARP), mono-ADPribosyltransferase (ARTs), and recently discovered sirtuin enzymes, NAD+ exerts potential biological effects. These enzymes modify proteins, regulating their function through ADP-ribosylation or deacetylation in the presence of NAD+. They are involved in various pathways, such as apoptosis, DNA repair, senescence, and endocrine signalling. These findings suggest that targeting these enzymes could be crucial in the treatment of cancer, diabetes, atherosclerosis, and other diseases.

NAMPT, also known as pre-B-cell colony-enhancing factor (PBEF1), is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide (NMN)in the salvage pathway of NAD+ biosynthesis in mammals. Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) converts NMN to NAD+. The expression of NAMPT is upregulated during activation of immune cells such as monocytes, macrophages, dendritic cells, T and B cells, as well as in amniotic epithelial cells upon stimulation with several inflammatory cytokines. NAMPT-specific inhibitor, FK866 was found to deplete intracellular NAD content, resulting in apoptotic cell death in many cancer cell lines without any DNA damaging effect. Recently, Nakahata K et al, demonstrated that NAMPT is required to modulate circadian gene expression and circadian oscillation of NAD+.

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) (EC is a central enzyme in NAD biosynthesis, transferring the adenylyl moiety of ATP to nicotinamide mononucleotide (NMN) or nicotinic acid mononucleotide (NaMN) resulting in the formation of NAD or NaAD and the release of pyrophosphate. As this reaction is reversible, the enzyme may in principle be used to form ATP and NMN from NAD and pyrophosphate. This enzyme could be a potential target for therapeutic applications because its activity is rather low in tumour cells.

CycLex NAMPT Colorimetric Assay Kit detects nicotinamide phosphoribosyltransferase (NAMPT) activity in recombinant NAMPT or endogenous NAMPT immunoprecipitated from cell extract.

Product CodeProduct Name 
CY-1251V2CycLex® NAMPT Colorimetric Assay Kit  
CY-1252V2CycLex® NMNAT Colorimetric Assay Kit Ver. 2
CY-1253V2CycLex® NAD+/NADH Colorimetric Assay Kit Ver.2


1. Miki A et al. Loss of aquaporin 9 expression adversely affects the survival of retinal ganglion cells. Am J Pathol. 182, 1727-39 (2013)
2. Adamovich Y et al. The protein level of PGC-1α, a key metabolic regulator, is controlled by NADH-NQO1. Mol Cell Biol. 33, 2603-13 (2013)

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Therapeutic Targets of the NAD+ Biosynthesis Pathway
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