Carnostatine hydrochloride (SAN9812 hydrochloride) is a potent and selective inhibitor of carnosinase 1 (CN1), with a K_i of 11 nM against human recombinant CN1, showing promise for the treatment of diabetic nephropathy (DN) [1].

CN1 (human):ki： 11 nM

Carnostatine inhibits CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. At a carnosine concentration of 200 μM, Carnostatine has an IC 50 value of 18 nM on human recombinant CN1, i.e., close to the K m of 190 μM [1].

Subcutaneous administration of 30 mg/kg Carnostatine (SAN9812) in human CN1 transgenic (TG) mice results in a sustained reduction in circulating CN1 activity. Simultaneous administration of Carnosine and Carnostatine significantly increases carnosine levels in plasma and kidney, up to 100-fold compared to untreated CN1-overexpressing mice [1]. Animal Model: Human carnosinase (CNDP1) transgenic mice on a BTBR wt/ob background [1] Dosage: 3 mg/kg i.v. or 30 mg/kg s.c. (Pharmacokinetic Analysis) Administration: Single bolus administration Result: Subcutaneous administration of 30 mg/kg led to a sustained reduction in circulating CN1 activity.