Amine N-methyltransferase Inhibitor

NNMTi is a potent nicotinamide N-methyltransferase (NNMT) inhibitor (IC₅₀=1.2 μM) and selectively binds to the NNMT substrate-binding site residues. NNMTi  promotes myoblast differentiation in vitro and enhances fusion and regenerative capacity of muscle stem cells (muSCs) in aged mice.

JBSNF-000088 (6-Methoxynicotinamide), a analog of nicotinamide (NA), is a potent and orally active Nicotinamide N-methyltransferase (NNMT) inhibitor with IC₅₀s of 1.8 µM, 2.8 µM, and 5.0 µM for human NNMT, monkey NNMT and mouse NNMT, respectively. JBSNF-000088 inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease.

NCGC00685960 is a Nicotinamide N-methyltransferase (NNMT) inhibitor with an IC₅₀ <10  nM. NCGC00685960 has potent antitumor activity. NCGC00685960 increases H3K27 trimethylation levels in ovarian cancer cells and inhibits α-SMA expression in NNMT-expressing ovarian fibroblasts. NCGC00685960 reduces 1-MNA levels, reverses SAM and H3K27 hypomethylation and significantly impairs collagen contractility in cancer-associated fibroblasts (CAFs). NCGC00685960 can be used for cancers research, such as ovarian cancer, breast cancer, colon cancer.

JBSNF-00002 free base is an orally active small molecule inhibitor of the tricyclic nicotinamide N-methyltransferase (NNMT) with IC₅₀ values for human, mouse and monkey sources of NNMT of 33, 210 and 190 nM respectively. JBSNF-00002 free base can reduce endogenous MNA levels in U2OS osteosarcoma cells, with its EC₅₀ being 2.5 μM. JBSNF-00002 free base exhibits significant anti-obesity and anti-diabetic activities in the diet-induced obesity (DIO) model. JBSNF-00002 free base can be used for the study of metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease.

LY 78335 (DCMB) is a brain-penetrant phenylethanolamine-N-methyltransferase (PNMT) inhibitor with a K_i of 0.09 μM. LY 78335 acts as an α₂-adrenoceptor inhibitor with an IC₅₀ of 10 μM. LY 78335 increases spontaneous locomotor activity in rats. LY 78335 increases extracellular concentration of 3-methoxy-4-hydroxyphenylglycol (MHPG) in rat hypothalamus. LY 78335 prevents growth hormone (GH) secretion in rats. LY 78335 can be used for the research of depression.

NNMT-IN-8 is a non-SAM-mimicking bisubstrate inhibitor and a selective methyltransferase NNMT inhibitor, with IC₅₀ values of 0.0084 μM and 0.0085 μM against human NNMT, and an IC₅₀ of 0.0072 μM against mouse NNMT. NNMT-IN-8 exhibits prominent renal distribution characteristics and moderate bioavailability in rodents. NNMT-IN-8 dose-dependently inhibits renal NNMT in renal fibrosis models, thereby exerting antifibrotic effects. NNMT-IN-8 can be used to investigate the mechanisms of renal fibrosis.

CC-410 is a selective Nicotinamide N-methyltransferase (NNMT) inhibitor with a human IC₅₀ value of 1.6 µM. CC-410 impairs terminal adipocyte differentiation via glucocorticoid signaling network deregulation, inhibits adipogenesis and lipid accumulation with time-sensitive activity limited to early adipogenesis stages. CC-410 can be used for the researches of early-onset obesity, glucocorticoid-induced obesity.

JBSNF-00002 hydrochloride is an orally active small molecule inhibitor of the tricyclic nicotinamide N-methyltransferase (NNMT) with IC₅₀ values for human, mouse and monkey sources of NNMT of 33, 210 and 190 nM respectively. JBSNF-00002 hydrochloride can reduce endogenous MNA levels in U2OS osteosarcoma cells, with its EC₅₀ being 2.5 μM. JBSNF-00002 hydrochloride exhibits significant anti-obesity and anti-diabetic activities in the diet-induced obesity (DIO) model. JBSNF-00002 hydrochloride can be used for the study of metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease.

1-(2,3-Dichlorophenyl)ethanamine hydrochloride is a phenylethanolamine N-methyltransferase (PNMT) inhibitor. 1-(2,3-Dichlorophenyl)ethanamine hydrochloride effectively reduces blood pressure of spontaneously hypertensive. 1-(2,3-Dichlorophenyl)ethanamine hydrochloride can be used for the research of blood pressure.

NNMT-IN-6 hydrochloride is a selective nicotinamide N-methyltransferase (NNMT) inhibitor with an IC₅₀ of 1.41 μM and a K_d of 5.55 μM. NNMT-IN-6 hydrochloride exhibits selectivity over PRMT1 and NSD2. NNMT-IN-6 hydrochloride inhibits cancer cell proliferation and reduces cellular N-methylnicotinamide (MNA) production. NNMT-IN-6 hydrochloride can be used for the research of oral cancer.

LL320 is a selective NNMT inhibitor with a K_i,app of 6.8 nM. LL320 exhibits interactions with RNMT, DPH₅, and SAHH.

NNMT-IN-3 (Compound 14) is a potent and selective nicotinamide N-methyltransferase (NNMT) inhibitor, with IC₅₀ values of 1.1 nM and 0.4 μM in cell-free and cell-based assays, respectively. NNMT-IN-3 can be used in the research of diseases such as obesity, type 2 diabetes and cancer.

JBSNF-00002 TFA is an orally active small molecule inhibitor of the tricyclic nicotinamide N-methyltransferase (NNMT) with IC₅₀ values for human, mouse and monkey sources of NNMT of 33, 210 and 190 nM respectively. JBSNF-00002 TFA can reduce endogenous MNA levels in U2OS osteosarcoma cells, with its EC₅₀ being 2.5 μM. JBSNF-00002 TFA exhibits significant anti-obesity and anti-diabetic activities in the diet-induced obesity (DIO) model. JBSNF-00002 TFA can be used for the study of metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease.

II399 is a potent, selective NNMT bisubstrate inhibitor containing an unconventional SAM mimic, with a K_i of 5.9 nM. II399 exhibits an explicit pattern of competitive inhibition for NAM. II399 occupies both the substrate and cofactor binding pockets. II399 has the potential for the research of cancers, metabolic, cardiovascular, and neurodegenerative diseases.

MS2734 is a dual-substrate NNMT inhibitor that acts as a SAM (HY-B0617) competitor and a non-competitor of Nicotinamide (HY-B0150), with an IC₅₀ of 14 μM and a K_d of 2.7 μM against hNNMT. MS2734 inhibits the methyltransferase activities of DOT1L (IC₅₀ 1.3 μM), PRMT7 (IC₅₀ 20 μM), BCDIN3D (IC₅₀ 40 μM) and SMYD2 (IC₅₀ 62 μM). MS2734 is applicable to research related to diabetes, obesity and various cancers.

4-Chloropyridine is a NNMT (Nicotinamide N-methyltransferase) substrate and suicide inhibition-based protein labeling scaffold precursor.4-Chloropyridine undergoes NNMT-catalyzed pyridine nitrogen methylation to increase C4 electrophilicity, enabling aromatic nucleophilic substitution by NNMT cysteine C159 for covalent NNMT modification and inactivation.4-Chloropyridine can be used for the research of various cancers.

NNMT-IN-6 is a selective nicotinamide N-methyltransferase (NNMT) inhibitor with an IC₅₀ of 1.41 μM and a K_d of 5.55 μM. NNMT-IN-6 hydrochloride exhibits selectivity over PRMT1 and NSD2. NNMT-IN-6 inhibits cancer cell proliferation and reduces cellular N-methylnicotinamide (MNA) production. NNMT-IN-6 can be used for the research of oral cancer.

NNMT-IN-5 (Compound 3-12) is a potent nicotinamide N-methyltransferase (NNMT) inhibitor (IC₅₀ = 47.9 ± 0.6 nM). NNMT-IN-5 also has an excellent selectivity profile over a panel of human methyltransferases. NNMT-IN-5 can be used for the research of cancer, diabetes, metabolic disorders, and neurodegenerative diseases.

JBSNF-00002 is an orally active small molecule inhibitor of the tricyclic nicotinamide N-methyltransferase (NNMT) with IC₅₀ values for human, mouse and monkey sources of NNMT of 33, 210 and 190 nM respectively. JBSNF-00002 can reduce endogenous MNA levels in U2OS osteosarcoma cells, with its EC₅₀ being 2.5 μM. JBSNF-00002 exhibits significant anti-obesity and anti-diabetic activities in the diet-induced obesity (DIO) model. JBSNF-00002 can be used for the study of metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease.

NNMT-IN-7 is a nicotinamide N-methyltransferase (NNMT) inhibitor with an IC₅₀ of 505.7 μM against human targets. NNMT-IN-7 inhibits the catalytic activity of NNMT, an enzyme responsible for mediating N-methylation modification of endogenous and exogenous xenobiotics. NNMT-IN-7 can be used in research related to obesity and type 2 diabetes.