Linagliptin (GSK2118436)

Synonyms: BI-1356

Linagliptin (GSK2118436) is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM and exhibits a 10,000-fold higher selectivity for DPP-4 than for other dipeptidyl peptidases such as DPP-2, DPP-8, and DPP-9. Linagliptin activates glomerular autophagy in a model of type 2 diabetes. DPP4 mediates ferroptosis in TP53-deficient CRC cells.

Linagliptin (GSK2118436) Chemical Structure

Linagliptin (GSK2118436) Chemical Structure

CAS: 668270-12-0

Selleck's Linagliptin (GSK2118436) has been cited by 16 Publications

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Purity & Quality Control

Batch: Purity: 99.99%
99.99

Linagliptin (GSK2118436) Related Products

Signaling Pathway

Choose Selective DPP Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human Caco-2 cells Function assay Inhibition of DPP4 in human Caco-2 cells after 1 hr, IC50=1 nM 18485703
CHO cells Function assay Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic M1 receptor expressed in CHO cells, IC50=0.295 μM 18052023
HEK293 cells Function assay Inhibition of mouse recombinant FAP expressed in HEK293 cells using Ala-Pro-p-nitroanilide as substrate incubated for 15 mins prior to substrate addition, IC50=0.37 μM 24900696
pig LLC-PK1 cells Function assay 100 μM Maximal inhibition of human P-glycoprotein expressed in pig LLC-PK1 cells assessed as reduction of [3H]digoxin substrate transport at 100 uM by liquid scintillation counting 23073734
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Biological Activity

Description Linagliptin (GSK2118436) is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM and exhibits a 10,000-fold higher selectivity for DPP-4 than for other dipeptidyl peptidases such as DPP-2, DPP-8, and DPP-9. Linagliptin activates glomerular autophagy in a model of type 2 diabetes. DPP4 mediates ferroptosis in TP53-deficient CRC cells.
Targets
Ferroptosis [4] DPP-4 [1]
(cell-free assay)
1 nM
In vitro
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]

Experimental Result Images Methods Biomarkers Images PMID
Western blot Cyclin D1 / p27 28177527
Growth inhibition assay Cell viability Cell viability 28177527
In Vivo
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). [1] 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. [3]

Animal Research Animal Models Male db/db mice
Dosages ≤1 mg/kg
Administration Administered via p.o.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04180813 Terminated
Diabetes Mellitus Type 2
Boehringer Ingelheim
March 4 2020 --
NCT02815644 Completed
Healthy
Boehringer Ingelheim
July 15 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 472.54 Formula

C25H28N8O2

CAS No. 668270-12-0 SDF Download Linagliptin (GSK2118436) SDF
Smiles CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 17 mg/mL ( (35.97 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 1 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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