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Amine N-methyltransferase inhibitors block enzymes that methylate the nitrogen atoms of amines. These enzymes take the methyl group from S-adenosylmethionine (SAM), the main methyl donor of the cell. Most listed compounds inhibit nicotinamide N-methyltransferase (NNMT), which converts nicotinamide into 1-methylnicotinamide. The human liver form of NNMT was cloned and biochemically characterized in 1994. A 2013 study showed that high NNMT activity in cancer cells consumes SAM and lowers histone methylation. In 2014, NNMT knockdown in mice protected against diet-induced obesity. JBSNF-000088, MS2734, II399 and NNMTi are among the listed NNMT inhibitors. LY 78335 and 1-(2,3-Dichlorophenyl)ethanamine hydrochloride inhibit phenylethanolamine N-methyltransferase (PNMT), the adrenal enzyme that converts norepinephrine into epinephrine.
Synonyms: 6-Methoxynicotinamide
JBSNF-000088 (6-Methoxynicotinamide), a analog of nicotinamide (NA), is a potent Nicotinamide N-methyltransferase (NNMT) inhibitor with IC50s of 1.8 µM, 2.8 µM, and 5.0µM for human NNMT, monkey NNMT and mouse NNMT, respectively.
NNMTi is a potent nicotinamide N-methyltransferase (NNMT) inhibitor with an IC₅₀ of 1.2 μM. It selectively binds to residues within the NNMT substrate-binding site. NNMTi promotes myoblast differentiation in vitro and enhances the fusion and regenerative capacity of muscle stem cells (muSCs) in aged mice, making it a promising compound for research into muscle regeneration and age-related muscle decline.
1-(2,3-Dichlorophenyl)ethanamine hydrochloride is a selective inhibitor of phenylethanolamine N-methyltransferase (PNMT). This compound effectively lowers blood pressure in spontaneously hypertensive models, making it a valuable tool for studying hypertension and its mechanisms. Researchers can utilize 1-(2,3-Dichlorophenyl)ethanamine hydrochloride to investigate the role of PNMT in blood pressure regulation and explore potential therapeutic avenues for hypertensive disorders.
Synonyms: DCMB
LY 78335 is a potent inhibitor of phenylethanolamine-N-methyltransferase (PNMT) with a Ki value of 0.09 μM. This compound also functions as an α₂-adrenoceptor antagonist, exhibiting an IC50 of 10 μM. Research indicates that LY 78335 enhances spontaneous locomotor activity in rat models and elevates the extracellular concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus. Additionally, it has been shown to inhibit growth hormone secretion, making LY 78335 a valuable tool for studies related to depression and neuroendocrine function.
JBSNF-000028 free base is a potent inhibitor of nicotinamide N-methyltransferase (NNMT), exhibiting IC50 values of 33 nM, 210 nM, and 190 nM for human, mouse, and monkey NNMT, respectively. This compound effectively reduces endogenous MNA levels in U2OS osteosarcoma cells, with an EC50 of 2.5 μM. JBSNF-000028 free base demonstrates notable anti-obesity and anti-diabetic effects in diet-induced obesity models, making it a valuable tool for researching metabolic disorders, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease.
NCGC00685960 is a potent inhibitor of Nicotinamide N-methyltransferase (NNMT) with an IC50 value of less than 10 nM. This compound exhibits significant antitumor properties by enhancing H3K27 trimethylation levels in ovarian cancer cells and reducing α-SMA expression in NNMT-expressing ovarian fibroblasts. Additionally, NCGC00685960 lowers 1-MNA levels and reverses SAM and H3K27 hypomethylation, effectively diminishing collagen contractility in cancer-associated fibroblasts (CAFs). It is a valuable reagent for cancer research applications.
MS2734 is a potent inhibitor of nicotinamide N-methyltransferase (NNMT), exhibiting an IC50 value of 14 μM against human NNMT (hNNMT). This compound effectively disrupts the methyltransferase activity of NNMT, making it a valuable tool for investigating the role of NNMT in metabolic disorders, neurodegenerative diseases such as Parkinson's disease, and various cancers characterized by elevated NNMT levels. Its utility in research applications extends to the exploration of obesity and diabetes-related mechanisms.
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NNMT-IN-6 hydrochloride is a potent inhibitor of nicotinamide N-methyltransferase (NNMT), exhibiting an IC50 value of 1.41 μM and a Kd of 5.6 μM. This compound demonstrates significant inhibitory effects on the proliferation of the HSC-2 human oral cancer cell line, making it a valuable tool for research in cancer biology and NNMT-related pathways. Its ability to modulate NNMT activity may provide insights into therapeutic strategies for diseases associated with altered methylation processes.
NNMT-IN-3 is a highly potent and selective inhibitor of nicotinamide N-methyltransferase (NNMT), exhibiting IC50 values of 1.1 nM in cell-free assays and 0.4 μM in cell-based assays. This compound plays a critical role in studying metabolic disorders and can be utilized in research involving obesity, type 2 diabetes, and cancer. Its specific inhibition of NNMT allows for detailed exploration of the enzyme's involvement in these significant diseases.
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II399 is a potent and selective inhibitor of nicotinamide N-methyltransferase (NNMT), featuring an unconventional S-adenosylmethionine (SAM) mimic, with a Ki value of 5.9 nM. This compound shows competitive inhibition for nicotinamide (NAM) by binding to both substrate and cofactor binding sites. II399 is valuable for research applications in cancer, metabolic disorders, cardiovascular diseases, and neurodegenerative conditions.
4-Chloropyridine is an inhibitor of Nicotinamide N-methyltransferase (NNMT), functioning as a substrate and a precursor for suicide inhibition-based protein labeling. This compound enhances the C4 electrophilicity of pyridine nitrogen through NNMT-catalyzed methylation, allowing for aromatic nucleophilic substitution at cysteine C159, resulting in covalent modification and inactivation of NNMT. 4-Chloropyridine is valuable for research into various cancers, facilitating studies on the role of NNMT in tumor biology.
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NNMT-IN-6 is a potent inhibitor of nicotinamide N-methyltransferase (NNMT), exhibiting an IC50 value of 1.41 μM and a dissociation constant (Kd) of 5.6 μM. This compound effectively inhibits cell proliferation in the HSC-2 human oral cancer cell line, making it a valuable tool for research focused on cancer biology and metabolism. Its specificity towards NNMT positions it as a promising candidate for further studies in therapeutic applications targeting NNMT-related pathways.
NNMT-IN-7 is a potent inhibitor of nicotine and nicotine metabolism transferase (NNMT) with an IC50 of 505.7 µM. This compound serves as a valuable tool for investigating the role of NNMT in metabolic and chronic diseases. Its use in research may provide insights into therapeutic strategies targeting metabolic disorders linked to altered NNMT activity.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is a selective inhibitor of phenylethanolamine N-methyltransferase (PNMT), exhibiting a Ki value of 0.3 μM. This compound is primarily utilized in research exploring psychiatric disorders associated with Alzheimer's disease and Parkinson's disease. Its mechanism of action makes it a valuable tool for studying the role of PNMT in neurodegenerative conditions.
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NNMT-IN-4 is a selective and uncompetitive inhibitor of nicotinamide N-methyltransferase (NNMT) with demonstrated membrane permeability. It exhibits IC50 values of 42 nM in biochemical assays and 38 nM in cell-based assays, indicating potent inhibition. With favorable pharmacokinetic and pharmacodynamic profiles, along with excellent oral bioavailability, NNMT-IN-4 serves as a valuable in vivo chemical probe for NNMT research applications.
LL320 is a selective inhibitor of Nicotinamide N-methyltransferase (NNMT), with an apparent Ki of 6.8 nM. This compound has demonstrated interactions with RNA N-methyltransferase (RNMT), diphthamide biosynthesis 5 (DPH5), and S-adenosylhomocysteine hydrolase (SAHH). LL320 is valuable for research applications focused on metabolic regulation, cancer biology, and the exploration of NNMT-related pathways.
