Products from BPS Bioscience require a minimum order value above 400€
Application: Study enzyme kinetics and screen small molecule inhibitors of NNMT for drug discovery and high throughput screening (HTS) applications.
Background: NNMT (nicotinamide N-methyltransferase) is a metabolic enzyme involved in the N-methylation of nicotinamide to MNA (1-methylnicotinamide), using SAM (S-adenosylmethionine) as the donor of the methyl group. It is found at high levels in the liver, and at lower levels in the brain, kidney, adipose tissue thyroid and pancreas. NAD+, an essential metabolite for generation of ATP by the mitochondrial respiration chain, and as substrate of proteins that include PARP1 [poly(ADP-ribose) polymerase 1] and sirtuins, is synthetized from tryptophan in the kynurenine pathway and from nicotinamide in a process that involves NAMPT (nicotinamide phosphoribosyltransferase) and NMNAT (nicotinamide adenine mononucleotide adenylyltransferase). The consumption of nicotinamide by NNMT has thus an impact on NAD+ production. NNMT is overexpressed in several diseases, including Alzheimer's and Parkinson's disease, atherosclerosis, obesity, fatty liver disease, COPD (chronic obstructive pulmonary disease), and cancer. Abnormal levels of NNMT have an impact on the methylation of the genome by reducing the amount of SAM available, and thus play an epigenic role. Studies in vitro indicate that NNMT can support tumor growth by decreasing apoptosis and necrosis and increasing ATP production. NNMT plays an oncogenic role and promotes drug resistance, not because it is essential for cancer development but by providing cancer cells with an advantage versus normal cells. NNMT has thus become an attractive therapeutical target for combinatory therapy, with investigation focusing on the discovery of small molecules targeting either its activity or its expression levels. NNMTi, an NNMT inhibitor, was able to reverse high-fat diet induced obesity in an animal model and the tumor burden in an ovarian cancer metastasis one, showing the potential of inhibiting NNMT. The development of NNMT inhibitors with higher selectivity and potency is going to open new avenues of treatment in oncology as a support for other therapies.
Contraindications: The final concentration of DMSO in the assay should not exceed 1%.Compounds that are fluorescent may interfere with the results, depending on their spectral excitation and emission properties.It is recommended that the compound alone is tested to determine any potential interference of the compound on the assay results.
Description: The NNMT Fluorogenic Assay Kit is designed to measure NNMT (Nicotinamide N-methyltransferase) activity for screening and profiling applications. The assay kit comes in a convenient 96-well format, with enough recombinant NNMT, substrate, cofactor, and assay buffer for 100 enzyme reactions.
Storage Stability: This assay kit will perform optimally for up to 6 months from date of receipt when the materials are stored as directed.
Uniprot: P40261
Warnings: Avoid freeze/thaw cycles
Biosafety Level: Not applicable (BSL-1)
References: Roberti A., et al., 2021 Molecular Metabolism 45:101165.
Parons R. and Facey P., 2021 Biomolecules 11(10):1418.
English
Deutsch
