Class

DPP-4inhibitors

Binding at DPP-4

Interaction with DPP-4 at various sites

Details

1

Vildagliptin & Saxagliptin

S1 & S2 Subsites

Ÿ Fundamental/basic interaction required for DPP-4 inhibition

Ÿ Cyanopyrrolidine moieties bind to S1

Ÿ Hydroxyadamantyl groups bind to S2

Ÿ Saxagliptin has 5-fold higher activity than Vildagliptin

2

Alogliptin

& Linagliptin

S1, S2, S1’ & S2’ subsites

Ÿ Alogliptin binds to S1, S2 & S1’

Ÿ Linagliptin binds to S1, S2, S1’ & S2’

Ÿ Linagliptin has 8-fold higher activity than Alogliptin

3

Sitagliptin

& Teneligliptin

S1,S2 & S2 extensive subsites

Ÿ Teneligliptin has 5 fold higher activity than Sitagliptin due to J-shaped anchor-lock domain, strong covalent bonds with DPP-4 & more extensive S2 extensive binding than Sitagliptin