Carnostatine (SAN9812) is a potent and selective carnosinase 1 (CN1) inhibitor with a K_i of 11 nM for human recombinant CN1. It may be used to increase renal carnosine concentration as a potential therapeutic modality for 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 injection of 30 mg/kg Carnostatine (SAN9812) consistently lowers CN1 activity in the bloodstream of human CN1 transgenic (TG) mice. When Carnostatine is administered alongside Carnosine, there is up to a 100-fold increase in Carnosine concentrations in both plasma and kidneys compared to CN1-overexpressing mice that have not received any treatment. The animal model used for this study involves human carnosinase (CNDP1) transgenic mice set against a BTBR wt/ob genetic background. The dosage tested includes 3 mg/kg intravenously (i.v.) or 30 mg/kg subcutaneously (s.c.), focusing on pharmacokinetic analysis. The results indicate that a single subcutaneous dose of 30 mg/kg effectively suppresses circulating CN1 activity.