Cadisegliatin (TTP-399) is a potential, orally active liver-selective glucokinase (GK) activator. Cadisegliatin has antihyperglycaemic activity. Cadisegliatin can be used for the research of type 2 diabetes[1][2].
Cadisegliatin (TTP-399) 增加大鼠肝细胞的葡萄糖代谢，15 nM 葡萄糖中乳酸和糖原的 EC50 值分别为 2.39 μM 和 2.64 μM [2].
TTP399（200 mg/kg，口服，口服）对禁食大鼠的血浆葡萄糖和胰岛素没有影响[2]。
TTP399（75 或 150 mg/kg，每天，持续 4 周）改善 ob/ob 小鼠模型的葡萄糖稳态[2]。
TTP399（50 mg/kg，每天，持续 13 周）在小型猪模型的口服葡萄糖耐量试验 (OGTT) 期间有效降低血浆葡萄糖[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.