Linagliptin-668270-12-0

Name:Linagliptin

CAS No.:668270-12-0

Molecular formula:C25H28N8O2

Molecular weight:472.54

EINECS:1308068-626-2

Melting point 202 ºC

Boiling point 661.2±65.0 °C(Predicted)

Density 1.39

Acidity coefficient (pKa) 10.01±0.20(Predicted)

Uses:Linagliptin is a novel, highly potent and selective dipeptidyl peptide-4 (DPP-4) inhibitor for the treatment of type 2 diabetes mellitus.

Biological Activity: Linagliptin (BI-1356) is a potent, selective DPP-4 inhibitor with an IC50 of 1 nM. It is more than 10,000-fold more selective for DPP-4 than other dipeptidyl peptidases such as DPP-2, DPP-8 and DPP9. DPP4 mediates iron death in TP53-deficient CRC cells.

In vitro studies

In vitro, Linagliptin exhibits potent inhibition of DPP-4 with low affinity for hERG channels and M1 receptors (IC50 295 nM). In vitro, Linagliptin acts as a competitive inhibitor with a K i of 1 nM and is 10,000-fold more selective for DPP-4 than for DPP-8, DPP-9, aminopeptidases N and P, prolyl oligopeptidase, trypsin, fibrin, and thrombin, and 90-fold more selective for fibroblast-activated proteins.

In vivo studies

In male Wistar rats, beagle dogs, and rhesus monkeys, Linagliptin exhibited efficient, sustained, and potent inhibitory activity against DPP-4, achieving more than 70% inhibition in all species when administered orally at a dose of 1 mg/kg. Linagliptin administered orally to db/db mice 45 minutes prior to oral glucose tolerance testing dose-dependently reduced blood glucose fluctuations from 0.1 mg/kg (15% inhibition) to 1 mg/kg (66% inhibition). By inhibiting DPP-4 activity, Linagliptin decreased the expression of the pro-inflammatory markers oxygenase-2 and macrophage inflammatory protein-2 and enhanced myofibroblast formation during wound healing in ob/ob mice.

Uses

Linagliptin, developed by Boehringer Ingelheim, was approved by the FDA on May 2, 2011 for use in combination with diet and exercise to improve the control of blood glucose levels in type 2 diabetic patients. Linagliptin improves glycemic control by inhibiting dipeptidyl peptidase-4 (DPP-4).