Small-molecule inhibitor: sitagliptin

Name

Common name: sitagliptin
Other names: Glactiv; Januvia; MK-0431; MK-431; Ono-5435; sitagliptun; Tesavel

History: Merck initiated phase III studies of this compound in the second quarter of 2004, and the further developments have been described by Kim et al. (2005) and Thornberry & Weber (2007).
Peptidases inhibited: Inhibits dipeptidyl-peptidase IV with IC(50) = 18 nM (Kim et al., 2005). There is little inhibition of the homologous peptidases, dipeptidyl-peptidase 8 and dipeptidyl-peptidase 9 (Thornberry & Weber, 2007).
Pharmaceutical relevance: Sitagliptin was developed as an agent for the treatment of type 2 diabetes (Pham et al. 2008).
DrugBank: DB01261

CID at PubChem: 4369359
ChEBI: 40237
Structure
Chemical/biochemical name: (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin -7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine
Formula weight: 407

Inhibitor class: This compound is one of the "gliptins" that are inhibitors of dipeptidyl-peptidase IV, and have been developed for potential use as drugs in the treatment of type 2 diabetes. These compounds suppress the degradation of the incretin hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide by dipeptidyl-peptidase IV. This helps to correct the defective insulin and glucagon secretion characteristic of this form of diabetes by stimulating insulin secretion and suppressing glucagon release (Chahal & Chowdhury, 2007; Thornberry & Gallwitz, 2009).