Small-molecule inhibitor: vildagliptin

Name

History: The development of vildagliptin (as NVP-LAF237) was described by Villhauer et al. (2003).
Peptidases inhibited: Vildagliptin is a selective inhibitor of dipeptidyl-peptidase IV (Brandt et al., 2005).
Mechanism: Inhibition is reversible. Vildagliptin is a slow-binding inhibitor with an association rate constant of 1.4x10⁵M^-1s^-1 and a K_i of 17 nM. It is a micromolar inhibitor for dipeptidyl-peptidase 8, but does not significantly inhibit a range of other peptidases (Brandt et al., 2005).
Pharmaceutical relevance: Vildagliptin is in clinical trials for type 2 diabetes. By inhibition of dipeptidyl-peptidase IV, and thus slowing the degradation of glucagon-like peptide 1, it reduces glycemia, sustains insulin levels, and reduces glucagon levels (Ahren et al., 2004).

Structure
Chemical/biochemical name: (2S)-([(3-hydroxyadamantan-1-yl)amino]acetyl)-pyrrolidine-2-carbonitrile

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).
Comment: Vildagliptin is a member of the class of N-substituted-glycyl-2-cyanopyrrolidine inhibitors of dipeptidyl-peptidase IV (Villhauer et al., 2003).
Reviews: Brandt et al. (2005)