| Name | Linagliptin |
| Description | Linagliptin (BI 1356) is a potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. |
| Cell Research | A total of 4.0×107 keratinocytes per well are seeded into 24-well plates. After reaching 50% confluence, cells are starved for 24 h with DMEM. Proliferation of cells is assessed by using 1 μCi/mL of [3H]methyl-thymidine in DMEM in the presence of 10% fetal bovine serum and increasing concentrations of linagliptin (3, 30, 300, or 600 nM) for 24 h. Cells are then washed twice with phosphate-buffered saline and incubated in 5% trichloroacetic acid at 4°C for 30 min, and the DNA is solubilized in 0.5mol/LNaOH for 30 min at 37°C. Finally, [3H]thymidine incorporation is determined. |
| Kinase Assay | EDTA plasma (20 μL) is diluted with 30 μL of DPP-4 assay buffer (100 mM Tris and 100 mM NaCl, adjusted to pH 7.8 with HCl) and mixed with 50 μL of H-Ala-Pro-7-amido-4-trifluoromethylcoumarin. The 200 mM stock solution in dimethylformamide is diluted 1:1000 with water to yield a final concentration of 100 μM. The plate is incubated at room temperature for 10 min, and fluorescence in the wells is determined by using a Victor 1420 Multilabel Counter at an excitation wavelength of 405 nm and an emission wavelength of 535 nm. For the detection of DPP-4 activity in wound lysates, 100 μg of protein from the respective wound lysates are used instead of 20 μL of plasma. Active GLP-1 is also detected from 100 μg of respective wound tissue samples and analyzed by using the Mouse/Rat Total Active GLP-1 Assay Kit. |
| In vitro | Linagliptin shows a potent inhibition effect against DPP-4 in vitro and a low affinity for hERG channel and M1 receptor (IC50 295 nM). [1] 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. [2] |
| In vivo | In male Wistar rats, Beagle dogs, and Rhesus monkeys, Linagliptin exhibits highly efficacious, long-lasting, and potent inhibitory activity against DPP-4 with over 70% inhibition for all three species after oral administration of 1 mg/kg. In db/db mice, oral administration of Linagliptin 45 min before an oral glucose tolerance test reduces plasma glucose excursion in a dose-dependent manner, achieving 15% inhibition at 0.1 mg/kg and 66% inhibition at 1 mg/kg. [1] By inhibiting DPP-4 activity, Linagliptin also reduces the expression of the proinflammatory markers cyclooxygenase-2 and macrophage inflammatory protein-2, and enhances myofibroblast formation in healing wounds from ob/ob mice. [3] |
| Storage | keep away from direct sunlight,store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 5.63 mg/mL (11.9 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 1 mg/mL (2.11 mM)
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| Keywords | Dipeptidyl Peptidase | BI-1356 | Inhibitor | Linagliptin | BI1356 | DPP | Autophagy | Ferroptosis | inhibit |
| Inhibitors Related | Stavudine | Sodium 4-phenylbutyrate | Hydroxychloroquine | Guanidine hydrochloride | Taurine | Curcumin | Paeonol | L-Cystine | Naringin | Gefitinib |
| Related Compound Libraries | Highly Selective Inhibitor Library | Bioactive Compound Library | EMA Approved Drug Library | Anti-Cancer Clinical Compound Library | Drug Repurposing Compound Library | FDA-Approved Drug Library | Anti-Cancer Approved Drug Library | Anti-Aging Compound Library | Bioactive Compounds Library Max | Anti-Cancer Drug Library |
United States
