JBSNF-000028 hydrochloride is a potent inhibitor of nicotinamide N-methyltransferase (NNMT) with IC50 values of 0.033 μM for human NNMT (hNNMT), 0.19 μM for monkey NNMT (mkNNMT), and 0.21 μM for mouse NNMT (mNNMT). This orally active compound is utilized in the study of metabolic disorders [1].

JBSNF-000028 hydrochloride demonstrates selective inhibition of NNMT activity, achieving an EC50 of 2.5 μM in U2OS cells (24 h) without exhibiting cytotoxic effects on HepG2 cells at concentrations ranging from 10 to 100 μM over a 72-hour period [1]. The compound specifically interacts with the nicotinamide pocket beneath a hairpin structural motif, intercalating between Tyr-204 (from Hairpin) and Leu-164 (from the central domain) [1]. Moreover, JBSNF-000028 hydrochloride shows no activity against a wide array of metabolic and safety-related targets [1].

JBSNF-000028 hydrochloride, administered orally at a dosage of 50 mg/kg twice daily, enhances glucose and lipid metabolism over a 27-day treatment in mice with diet-induced obesity (DIO) and improves glucose tolerance in NNMT knockout mice with DIO when given for 4 weeks [1].