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Linagliptin (GSK2118436) DPP inhibitor

Name: Linagliptin (GSK2118436)
Brand: Selleck Chemicals
SKU: S3031
Availability: InStock
Rating: 5 (21 reviews)

Cat.No.S3031

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. This compound activates glomerular autophagy in a model of type 2 diabetes and mediates ferroptosis in TP53-deficient CRC cells via DPP4.

Chemical Structure

Molecular Weight: 472.54

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Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	HDAC Caspase Proteasome Secretase MMP HCV Protease Cysteine Protease Tyrosinase HIV Protease Serine Protease
Other DPP Inhibitors	Talabostat (Val-boroPro, PT-100) Mesylate Puromycin aminonucleoside MK-3102 (Omarigliptin) Brensocatib Lobeliae Chinensis Extract Teneligliptin Hydrobromide Hydrate Anagliptin Trelagliptin Teneligliptin hydrobromide Trelagliptin succinate

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Activity Description
human Caco-2 cells	Function assay		Inhibition of DPP4 in human Caco-2 cells after 1 hr, IC50=1 nM
CHO cells	Function assay		Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic M1 receptor expressed in CHO cells, IC50=0.295 μM
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
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
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 24 mg/mL (50.78 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 7 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5% DMSO 1 40% PEG300 2 5%Tween80 3 50% ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.200mg/ml (2.54mM)	Taking the 1 mL working solution as an example, add 50 μL of 24 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.600mg/ml (1.27mM)	Taking the 1 mL working solution as an example, add 50 μL of 12 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	472.54	Formula	C₂₅H₂₈N₈O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	668270-12-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	BI-1356			Smiles	CC#CCN1C2=C(N=C1N3CCCC(C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C

Mechanism of Action

Targets/IC₅₀/Ki	Ferroptosis DPP-4 (cell-free assay) 1 nM
In vitro	Linagliptin (GSK2118436) shows a potent inhibition effect against DPP-4 in vitro and a low affinity for hERG channel and M1 receptor (IC50 295 nM). It acts as a competitive inhibitor with a K_i 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.
In vivo	Linagliptin (GSK2118436) shows a highly efficacious, long-lasting, and potent inhibitory activity against DPP-4 in male Wistar rats, Beagle dogs, and Rhesus monkeys, with more than 70% inhibition for all three species after oral administration of 1 mg/kg. When administered orally to db/db mice 45 min before an oral glucose tolerance test, it 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, this compound 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/18052023/ [2] https://pubmed.ncbi.nlm.nih.gov/18223196/ [3] https://pubmed.ncbi.nlm.nih.gov/22493041/ [4] https://pubmed.ncbi.nlm.nih.gov/28813679/

Applications

Methods	Biomarkers	Images	PMID
Western blot	Cyclin D1 / p27		28177527
Growth inhibition assay	Cell viability Cell viability		28177527

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04180813	Terminated	Diabetes Mellitus Type 2	Boehringer Ingelheim	March 4 2020	--

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