Trelagliptin (succinate)

Trelagliptin (SYR-472) succinate is a potent, orally active and highly selective DPP-4 inhibitor with an IC₅₀ of 4 nM. Trelagliptin succinate improves glycemic control in vivo and can be used for the study of type 2 diabetes mellitus (T2DM)^[1]. IC50 & Target: IC50: 4 nM (DPP-4)^[1] In Vitro: Dipeptidyl peptidase-4 (DPP-4) is one of the widely explored novel targets for type 2 diabetes mellitus (T2DM)?strategy to preserve the endogenous glucagon like peptide (GLP)-1 activity by inhibiting the DPP-4 action^[1].
Trelagliptin exhibits potent inhibitory activity toward DPP-4 prepared from Caco-2 cells with an IC₅₀?value of 5.4 nM. Trelagliptin also inhibits human, dog, and rat plasma DPP-4 activity with IC₅₀?values of 4.2 nM, 6.2 nM, and 9.7 nM, respectively^[2].
Trelagliptin is highly selective for DPP-4 and displays IC₅₀?values >100,000 nM corresponding to >10,000-fold selectivity over DPP-2, DPP-8, DPP-9, PEP and FAPα activities. Trelagliptin shows DPP4 selective about 4- and 12-fold more potent than alogliptin (HY-A0023) and sitagliptin (HY-13749), respectively^[2].
In Vivo: Trelagliptin (oral gavage; 7 mg/kg; single dose) shows sustained PD effect in dogs and gives >80% inhibition of DPP-4 activity even after 24h^[1].
Trelagliptin (oral gavage; 3 mg/kg; single dose; 60 min prior to oral glucose) significantly improves the glucose tolerance capacity by decreasing the AUC_0?120min of 19.3% compared with the vehicle group in ob/ob mice^[3].
Trelagliptin (oral gavage; 10 mg/kg; once a week; 8 weeks) caused significant reductions in fasting blood glucose (FBG) levels, and the average reduction during the entire treatment period is 16.8% compared to the control.It also increases insulin level and raised it by 1.7-fold in AUC_0?120min in ob/ob mice^[3].