A small molecule inhibitor of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and bench research with no human participants
PubMed 29483571 · doi:10.1038/s41598-018-22081-7
What was done
The authors investigated JBSNF-000088, a small-molecule nicotinamide analog and inhibitor of nicotinamide N-methyltransferase (NNMT). They evaluated its metabolic effects in animal models including high-fat diet (HFD)-induced obese mice, NNMT knockout mice on HFD, and genetically obese/diabetic ob/ob and db/db mice. Mechanism of action was evaluated via co-crystal structure analysis and plasma metabolite detection.
What was found
In HFD-induced obese mice, JBSNF-000088 treatment reduced body weight, improved insulin sensitivity, and normalized glucose tolerance to lean control levels. These effects did not occur in NNMT knockout mice on HFD. In ob/ob and db/db mice, the compound improved glucose handling to a lesser extent without reducing body weight. Co-crystal structure analysis and plasma profiling identified the N-methylated product of JBSNF-000088, indicating it acts as a slow-turnover substrate analog. No specific numerical values were reported in the abstract.
Why it matters
The study identifies a small-molecule NNMT inhibitor capable of improving insulin sensitivity, glucose tolerance, and body weight in preclinical models of diet-induced metabolic disease.
Limits
All findings are derived from rodent models and biochemical structural analyses, with unproven efficacy and safety in humans. The abstract omits sample sizes, dosages, exposure durations, and numerical effect sizes.
Cited by
- supports JBSNF-000088 is a molecule that inhibits the NNMT enzyme.