JBSNF-000088 is an inhibitor of nicotinamide N-methyltransferase (NNMT; IC50s = 1.8, 2.8, and 5 ?M for human, monkey, and mouse NNMT, respectively).1 It inhibits NNMT and reduces 1-methyl-nicotinamide (MNA) levels in U2OS and 3T3L1 cells (IC50s = 1.6 and 6.3 ?M, respectively). JBSNF-000088 (50 mg/kg) reduces visceral white adipose tissue (WAT) MNA levels, body weight, fed blood glucose levels, and plasma and liver triglyceride levels, and improves oral glucose tolerance in a mouse model of diet-induced obesity (DIO). It also improves glucose tolerance, without affecting body weight, in the ob/ob and db/db mouse models of insulin resistance and diabetes, respectively.
1.Kannt, A., Rajagopal, S., Kadnur, S.K., et al.A small molecule inhibitor of nicotinamide N-methyltransferase for the treatment of metabolic disordersSci. Rep.8(1)3660(2018)