{2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid

Cadisegliatin (TTP-399) is a potential liver-selective glucokinase (GK) activator for type 2 diabetes and has antihyperglycaemic activity[1][2].

Signaling Pathways >> Metabolic Enzyme/Protease >> Glucokinase

Research Areas >> Metabolic Disease

Cadisegliatin (TTP-399) increases glucose metabolism in rat hepatocytes, the EC50 values of lactate and glycogen in 15 mM glucose are 2.39 μM and 2.64 μM, respectively[2].

TTP399 (200 mg/kg, per os, p.o.) has no effect on plasma glucose and insulin in fasted rats. TTP399 (75 or 150 mg/kg, per day, for 4 weeks) improves glucose homeostasis in ob/ob mouse model. TTP399 (50 mg/kg, per day, for 13 weeks) is effective in reducing plasma glucose during an oral glucose tolerance test (OGTT) in minipigs model[2]. Animal Model: Nondiabetic fasted rats[2] Dosage: 200 mg/kg Administration: 200 mg/kg, per os (p.o.) Result: Did not change the insulin and glucose concentrations in plasma. Animal Model: ob/ob mouse model[2] Dosage: 75 or 150 mg/kg Administration: 75 or 150 mg/kg, per day, for 4 weeks Result: Reduced the expression of HbA1c, blood glucose concentrations, lactate concentrations and liver glycogen depots. Improved the lipid profile, reduced plasma, liver TG concentrations and the weight gain at the highest dose. Animal Model: Gottingen minipigs[2] Dosage: 50 mg/kg Administration: 50 mg/kg, per day, for 13 weeks Result: Eliminated the blood glucose excursion in Minipigs.

[1]. International Nonproprietary Names for Pharmaceutical Substances (INN)

[2]. Adrian Vella, et al. Targeting hepatic glucokinase to treat diabetes with TTP399, a hepatoselective glucokinase activator. Sci Transl Med. 2019 Jan 16;11(475):eaau3441.