| Title : Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism - Grimshaw_2016_PLoS.One_11_e0157509 |
| Author(s) : Grimshaw CE , Jennings A , Kamran R , Ueno H , Nishigaki N , Kosaka T , Tani A , Sano H , Kinugawa Y , Koumura E , Shi L , Takeuchi K |
| Ref : PLoS ONE , 11 :e0157509 , 2016 |
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Abstract :
Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4- and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t1/2 for dissociation approximately 30 minutes). X-ray diffraction data indicated a non-covalent interaction between dipeptidyl peptidase and trelagliptin. Taken together, potent dipeptidyl peptidase inhibition may partially contribute to sustained efficacy of trelagliptin. |
| PubMedSearch : Grimshaw_2016_PLoS.One_11_e0157509 |
| PubMedID: 27328054 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | Trelagliptin |
| Gene_locus | Trelagliptin human-DPP4 |
| Structure | Trelagliptin human-DPP4 5KBY |
Grimshaw CE, Jennings A, Kamran R, Ueno H, Nishigaki N, Kosaka T, Tani A, Sano H, Kinugawa Y, Koumura E, Shi L, Takeuchi K (2016)
Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism
PLoS ONE
11 :e0157509
Grimshaw CE, Jennings A, Kamran R, Ueno H, Nishigaki N, Kosaka T, Tani A, Sano H, Kinugawa Y, Koumura E, Shi L, Takeuchi K (2016)
PLoS ONE
11 :e0157509