5-Amino-1MQ Research

Chanvillard L, Lantermans HC, Wall C, Thevenet J, Butter LM, Tauzin L et al.

Chronic kidney disease (CKD) is projected to become the fifth leading cause of mortality by 2040. Tubular senescence drives kidney fibrosis, but current treatments do not target senescent cells. Here, we identify nicotinamide-N-methyltransferase (NNMT) as a critical mediator of tubular senescence...

Dong G, Choi J, Li Y, Muller DC, Li Z, Luo YE et al.

Peripheral artery disease (PAD) impairs limb perfusion, walking ability, and increases the risk of amputation. Although current therapies reduce cardiovascular events, few interventions improve skeletal muscle function in PAD. Nicotinamide adenine dinucleotide (NAD+) metabolism is disrupted in PA...

Heide J, Bilecz AJ, Patnaik S, Allega MF, Donle L, Yang K et al.

Cancer-associated fibroblasts (CAFs) have a pivotal cancer-supportive role, yet CAF-targeted therapies are lacking1,2. Here, using spatial transcriptomics and single-cell RNA sequencing, we investigate the role of nicotinamide N-methyltransferase (NNMT) in high-grade serous ovarian cancer. Mechan...

Hou Z, Wang Z, Yang F, Han X, Li L, Liu H et al.

Kinase inhibitors have achieved great success in targeted cancer therapy, yet the evident limitations in their effectiveness persist due to therapeutic resistance. To gain insight into the molecular mechanisms and thwart resistance, we profiled the time-resolved nascent protein perturbations in r...

Li S, Rodrigues PG, Chakraborty AD, Correia C, Schouten EM, Strömstedt M et al.

HFpEF is a major and global disease with limited treatment options and novel therapeutics are eagerly awaited. A potential treatment option may be Nicotinamide N-methyltransferase (NNMT) inhibition. This study aimed to investigate the cardiac protective effects of the NNMT enzyme inhibitor AMO-NA...

Yang Y, Li F, Li Y, Li X, Zhao Z, Zhang N et al.

We aim to explore the potential of nicotinamide n-methyltransferase (NNMT) as a sensitive marker of renal tubular injury and the possibility of an NNMT inhibitor to combine with sodium-glucose cotransporter 2 (SGLT2) inhibitor to protect proximal tubular epithelium in vivo and in vitro model of T...

Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H

To assess the effects of a small-molecule nicotinamide N-methyltransferase (NNMT) inhibitor, 5A1MQ, on body composition, metabolic variables, fatty liver pathologies, and circulating biomarkers in diet-induced obese (DIO) mice, and characterize its plasma pharmacokinetics (PK) and tissue distribu...

Yang M, Wang B, Hou W, Zeng H, He W, Zhang XK et al.

This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression a...

Ye Q, Xu G, Huang H, Pang S, Xie B, Feng B et al.

Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD....

Iyamu ID, Zhao T, Huang R

Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme implicated in multiple diseases, making it a promising therapeutic target. Building upon our recently reported NNMT inhibitor II399, we systematically investigate the structure-activity relationship by designing and synthesizing a seri...

Harikrishna AS, Venkitasamy K

Human nicotinamide N-methyltransferase (hNNMT) is a cytosolic enzyme associated in the phase-II metabolism, belonging to the S-adenosyl-L-methionine (SAM)-dependent methyltransferases family. Overexpression of hNNMT was observed in diseases such as metabolic disorders and different types of cance...

Li Y, Yang B, Miao H, Liu L, Wang Z, Jiang C et al.

Nicotinamide N -methyltransferase (NNMT), an enzyme responsible for the methylation of nicotinamide, is involved in many metabolic pathways in adipose tissue and the liver. However, the role of NNMT in editing the tumor immune microenvironment is not well understood.Here, we identified that NNMT ...

Huang H, Zhao G, Cardenas H, Valdivia AF, Wang Y, Matei D et al.

Development of resistance to platinum (Pt) in ovarian cancer remains a major clinical challenge. Here we focused on identifying epitranscriptomic modifications linked to Pt resistance. Fat mass and obesity-associated protein (FTO) is a N6-methyladenosine (m6A) RNA demethylase that we recently des...

Barrows RD, Jeffries DE, Vishe M, Tukachinsky H, Zheng SL, Li F et al.

NNMT uses SAM as a cofactor to catalyze the methylation of nicotinamide, producing 1-methylnicotinamide. Recent studies have shown that NNMT upregulation in cancer-associated fibroblasts (CAFs) is required to maintain the CAF phenotype in high-grade serous carcinoma. These observations suggest th...

Kushavah U, Panigrahi L, Ahmed S, Siddiqi MI

Nicotinamide N-methyltransferase (NNMT) is a protein coding gene, which methylates the nicotinamide (NA) (vitamin B3) to produce 1-methylnicotinamide (MNA). Several studies have suggested that the overexpression of NNMT is associated with different metabolic disorders like obesity and type-2 diab...

Li XY, Pi YN, Chen Y, Zhu Q, Xia BR

Cancer cells typically exhibit a tightly regulated program of metabolic plasticity and epigenetic remodeling to meet the demand of uncontrolled cell proliferation. The metabolic-epigenetic axis has recently become an increasingly hot topic in carcinogenesis and offers new avenues for innovative a...

Reustle A, Menig LS, Leuthold P, Hofmann U, Stühler V, Schmees C et al.

The metabolic enzyme nicotinamide-N-methyltransferase (NNMT) is highly expressed in various cancer entities, suggesting tumour-promoting functions. We systematically investigated NNMT expression and its metabolic interactions in clear cell renal cell carcinoma (ccRCC), a prominent RCC subtype wit...

Wang J, Liu X, Huang Y, Li P, Yang M, Zeng S et al.

Activating mutations of epidermal growth factor receptor (EGFR) contributes to the progression of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for NSCLC patients with EGFR-mutations. However, acquired resistance to the...

Dimet-Wiley A, Wu Q, Wiley JT, Eswar A, Neelakantan H, Savidge T et al.

Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch...

Gao Y, van Haren MJ, Buijs N, Innocenti P, Zhang Y, Sartini D et al.

Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NN...