Trelagliptin succinate

Trelagliptin (SYR-472) is a long acting dipeptidyl peptidase-4 (DPP-4) inhibitor that is being developed for the treatment of type 2 diabetes (T2D) . (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.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.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. (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.Trelagliptin (oral gavage; 3 mg/kg; single dose; 60 min prior to oral glucose) significantly improves the glucose tolerance capacity by decreasing the AUC0 120min of 19.3% compared with the vehicle group in ob/ob mice.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 AUC0 120min in ob/ob mice.

1029877-94-8

SYR-472

Pharmacology & Drug Discovery

>98% (HPLC)

DMSO: 10 mM

CN1C (=O) C=C (N (C1=O) CC2=C (C=CC (=C2) F) C#N) N3CCC[C@H] (C3) N.C (CC (=O) O) C (=O) O

C22H26FN5O6

475.47

Storage temperature: -20°C. Stability: ≥ 2 years