product name Linagliptin
Description: Linagliptin (also known as BI-1356) is a novel, highly potent, selective, and competitive DPP-4 inhibitor with IC50 of 1 nM. DPP-4 plays a major role in the degradation of incretins such as GLP-1 which is of great importance in the process of glucose metabolism. Under physiological conditions, GLP-1 is truncated by DPP-4 rapidly, which is located on the capillary endothelium proximal to the L-cells where GLP-1 is secreted in the ileum.
References: J Med Chem. 2007 Dec 27;50(26):6450-3; J Pharmacol Exp Ther. 2008 Apr;325(1):175-82.
472.54
Formula
C25H28N8O2
CAS No.
668270-12-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 17 mg/mL (36.0 mM)
Water: <1 mg/mL
Ethanol: 1 mg/mL (2.1 mM)
Solubility (In vivo)
0.5% hydroxyethyl cellulose: 30 mg/mL
Synonyms
BI-1356
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19414841
| In Vitro |
In vitro activity: Linagliptin shows a potent inhibition effect against DPP-4 in vitro and a low affinity for hERG channel and M1 receptor (IC50 295 nM). Linagliptin acts as a competitive inhibitor with a Ki of 1 nM, and also shows 10,000-fold more selectivity for DPP-4 than DPP-8, DPP-9, amino-peptidases N and P, prolyloligopeptidase, trypsin, plasmin, and thrombin, and 90-fold more selectivity than fibroblast activation protein in vitro. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | In male Wistar rats, Beagle dogs, and Rhesus monkeys, Linagliptin shows a highly efficacious, long-lasting, and potent inhibitory activity against DPP-4 by more than 70% inhibition for all three species after oral administration of 1 mg/kg. Oral administration of Linagliptin to db/db mice 45 min before an oral glucose tolerance test reduces plasma glucose excursion in a dose-dependent manner from 0.1 mg/kg (15% inhibition) to 1 mg/kg (66% inhibition). By inhibiting DPP-4 activity, Linagliptin reduces the expression of the proinflammatory markers cyclooxygenase-2 and macrophage inflammatory protein-2, and enhances the formation of myofibroblasts in healing wounds from ob/ob mice. |
| Animal model | Male db/db mice |
| Formulation & Dosage | Dissolved in 0.1 N HCl and subsequently diluted with a 0.5% aqueous hydroxyethylcellulose solution (final HCl concentration 3 mM); 1 mg/kg; p.o. administration |
| References | J Med Chem. 2007 Dec 27;50(26):6450-3; J Pharmacol Exp Ther. 2008 Apr;325(1):175-82. |
