Dipeptidyl peptidase IV Inhibitor III

Dipeptidyl peptidase IV is a key enzyme involved in the regulation of incretin hormone levels in the gastrointestinal tract. Incretin hormones, such as glucagon like peptide (GLP-1) and glucose-dependent insulinotopic hormone (GIP) / gastoric inhibitory peptide, cause the glucose stimulated release of insulin. This allows the endocrine system to preemptively stimulate release insulin in response to ingestion of high sugar foods. Type 2 diabetics demonstrate a greatly reduced incretin induced insulin release response.

This response in hyperglycemic conditions is counterbalanced by the rapid rate of degradation of these incretin hormones by dipeptidyl peptidase IV in normal conditions. Inhibition of dipeptidyl peptidase IV results in longer lifetime of the incretin hormones in the GI tract and thus prolonged stimulation of insulin production. Specific dipeptidyl peptidase inhibitors are actively being explored as drug targets for treating type 2 diabetes and several candidates are actively in clinical trial.

Dipeptidyl peptidase IV Inhibitor III is an orally bioavailable dicyanopyrrolidine compound that acts as a slow-binding and active site-targeting inhibitor of Dipeptidyl peptidase IV (IC50 = 106 nM using recombinant human DPP IV

Dipeptidyl peptidase IV is a key enzyme involved in the regulation of incretin hormone levels in the gastrointestinal tract. Incretin hormones, such as glucagon like peptide (GLP-1) and glucose-dependent insulinotopic hormone (GIP) / gastoric inhibitory peptide, cause the glucose stimulated release of insulin. This allows the endocrine system to preemptively stimulate release insulin in response to ingestion of high sugar foods. Type 2 diabetics demonstrate a greatly reduced incretin induced insulin release response.

This response in hyperglycemic conditions is counterbalanced by the rapid rate of degradation of these incretin hormones by dipeptidyl peptidase IV in normal conditions. Inhibition of dipeptidyl peptidase IV results in longer lifetime of the incretin hormones in the GI tract and thus prolonged stimulation of insulin production. Specific dipeptidyl peptidase inhibitors are actively being explored as drug targets for treating type 2 diabetes and several candidates are actively in clinical trial.