Linagliptin
Based on 15 publication(s) in Google Scholar
Linagliptin is a highly potent, selective DPP-4 inhibitor with IC50 of 1 nM.
For research use only. We do not sell to patients.
- Purity: 99.74%
- CAS No.: 668270-12-0
- Formula: C25H28N8O2
- Molecular Weight:472.54
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
Publications Citing Use of MedChemExpress (MCE) Linagliptin
More- Adv Sci (Weinh). 2026 Jul;13(38):e16904. [Abstract]
- J Clin Invest. 2025 Sep 16:e192011. [Abstract]
- Pharmacol Res. 2026 May 18:230:108249. [Abstract]
- Cell Rep. 2023 Feb 28;42(2):112105. [Abstract]
- Neural Regen Res. 2023 Aug;18(8):1818-1826. [Abstract]
- Talanta. 2025 Mar 20:292:127992. [Abstract]
- Biochem Pharmacol. 2018 Oct:156:312-321. [Abstract]
- Int J Mol Sci. 2024 Mar 5;25(5):3008. [Abstract]
- Molecules. 2022 Apr 12;27(8):2478. [Abstract]
- Neurochem Int. 2020 Feb;133:104616. [Abstract]
- Sci Rep. 2017 Jun 28;7(1):4351. [Abstract]
- Toxicol Appl Pharmacol. 2022 Mar 1:438:115906. [Abstract]
- BMC Pharmacol Toxicol. 2025 Dec 8;26(1):208. [Abstract]
- bioRxiv. 2025 Feb 6:2025.01.31.635976. [Abstract]
- Research Square Preprint. 2021 Oct.
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Cell Proliferation/Viability Assay
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In Vivo Efficacy Study
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IHC
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IF
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Cell Proliferation/Viability Assay
Biological Activity
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DPP-4 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| Caco-2 | IC50 |
1 nM
Compound: 1, BI 1356
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Inhibition of human DPP4 in Caco-2 cells by fluorescene assay
Inhibition of human DPP4 in Caco-2 cells by fluorescene assay
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[PMID: 18052023] |
| Caco-2 | IC50 |
1 nM
Compound: B1 1356
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Inhibition of DPP4 in human Caco-2 cells after 1 hr
Inhibition of DPP4 in human Caco-2 cells after 1 hr
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[PMID: 18485703] |
| Caco-2 | IC50 |
1 nM
Compound: XV, Trajenta
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Inhibition of DPP4 in human Caco2 cells using H-Ala-Pro-7-amido-4-trifluoromethylcoumarin as substrate after 1 hr by fluorescence assay
Inhibition of DPP4 in human Caco2 cells using H-Ala-Pro-7-amido-4-trifluoromethylcoumarin as substrate after 1 hr by fluorescence assay
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[PMID: 23623674] |
| CHO | IC50 |
295 nM
Compound: 1, BI 1356
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Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic M1 receptor expressed in CHO cells
Displacement of [N-methyl-3H]scopolamine from human recombinant muscarinic M1 receptor expressed in CHO cells
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[PMID: 18052023] |
| HEK293 | IC50 |
>100 μM
Compound: Linagliptin
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Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]E-sul substrate uptake by liquid scintillation counting
Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]E-sul substrate uptake by liquid scintillation counting
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[PMID: 23073734] |
| HEK293 | IC50 |
>100 μM
Compound: Linagliptin
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Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]E217betaG substrate uptake by liquid scintillation counting
Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells assessed as reduction of [3H]E217betaG substrate uptake by liquid scintillation counting
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[PMID: 23073734] |
| HEK293 | IC50 |
0.37 μM
Compound: 2
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Inhibition of recombinant mouse FAP purified from HEK293 cell supernatant using Ala-Pro-p-nitroanilide as substrate by spectrophotometry
Inhibition of recombinant mouse FAP purified from HEK293 cell supernatant using Ala-Pro-p-nitroanilide as substrate by spectrophotometry
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[PMID: 24617858] |
| HEK293 | IC50 |
0.37 μM
Compound: 2,BI 1356, linagliptin, Tradjenta
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Inhibition of mouse recombinant FAP expressed in HEK293 cells using Ala-Pro-p-nitroanilide as substrate incubated for 15 mins prior to substrate addition
Inhibition of mouse recombinant FAP expressed in HEK293 cells using Ala-Pro-p-nitroanilide as substrate incubated for 15 mins prior to substrate addition
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[PMID: 24900696] |
| HEK293 | IC50 |
41 μM
Compound: Linagliptin
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Inhibition of OCT1 (unknown origin) expressed in HEK293 cells assessed as reduction of [14C]metformin substrate uptake at 100 uM by liquid scintillation counting
Inhibition of OCT1 (unknown origin) expressed in HEK293 cells assessed as reduction of [14C]metformin substrate uptake at 100 uM by liquid scintillation counting
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[PMID: 23073734] |
| HEK293 | IC50 |
45 μM
Compound: Linagliptin
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Inhibition of OCT1 (unknown origin) expressed in HEK293 cells assessed as reduction of [ethyl 1-14C]TEA substrate uptake at 100 uM by liquid scintillation counting
Inhibition of OCT1 (unknown origin) expressed in HEK293 cells assessed as reduction of [ethyl 1-14C]TEA substrate uptake at 100 uM by liquid scintillation counting
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[PMID: 23073734] |
| HEK293 | IC50 |
80 μM
Compound: Linagliptin
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Inhibition of OCT2 (unknown origin) expressed in HEK293 cells assessed as reduction of [14C]metformin substrate uptake at 100 uM by liquid scintillation counting
Inhibition of OCT2 (unknown origin) expressed in HEK293 cells assessed as reduction of [14C]metformin substrate uptake at 100 uM by liquid scintillation counting
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[PMID: 23073734] |
| LLC-PK1 | IC50 |
66.1 μM
Compound: Linagliptin
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Inhibition of human P-glycoprotein expressed in pig LLC-PK1 cells assessed as reduction of [3H]digoxin substrate transport from basolateral to apical side by liquid scintillation counting
Inhibition of human P-glycoprotein expressed in pig LLC-PK1 cells assessed as reduction of [3H]digoxin substrate transport from basolateral to apical side by liquid scintillation counting
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[PMID: 23073734] |
Linagliptin inhibits DPP-4 activity in vitro in several independent experiments with IC50 values of 0.4, 0.5, 0.9, and 1.1 nM (mean IC50, approximately 1 nM). Linagliptin inhibits FAP with an IC50 of 89 nM (approximately 90-fold selectivity versus DPP-4)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 668270-12-0
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Appearance Solid
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Molecular Weight 472.54
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Formula C25H28N8O2
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Color White to off-white
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SMILES
O=C1N(C2=C(C(N1CC3=NC(C)=C4C=CC=CC4=N3)=O)N(CC#CC)C(N5CCC[C@@H](N)C5)=N2)C
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Synonyms
BI 1356
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (15)
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Journal Impact Factor
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Most Recent
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Adv Sci (Weinh)
2026 Jul;13(38):e16904. PMID: 41984505 -
J Clin Invest
Fatty acid transport protein-2 inhibition enhances glucose tolerance through α-cell-mediated GLP-1 secretion. [Abstract]2025 Sep 16:e192011. PMID: 40956612 -
Pharmacol Res
Targeted MSC therapy restores implantation by spatially reconstituting the RSPO1 niche via IL10-CXCL12 signaling. [Abstract]2026 May 18:230:108249. PMID: 42155786 -
Cell Rep
Dipeptidylpeptidase 4 promotes survival and stemness of acute myeloid leukemia stem cells. [Abstract]2023 Feb 28;42(2):112105. PMID: 36807138
Linagliptin purchased from MedChemExpress. Usage Cited in: Cell Rep. 2023 Feb 28;42(2):112105. [Abstract]
DPP4 inhibitors (Linagliptin 200 nM, vildagliptin 300 nM) suppress the growth of THP1 cells (n = 3 wells).
Linagliptin purchased from MedChemExpress. Usage Cited in: Cell Rep. 2023 Feb 28;42(2):112105. [Abstract]
Linagliptin (Lgp, 1 mg/kg; i.p.; once daily for 20 days) led to significantly increased survival of AML cell-transplanted mice due to slower AML development, similar to Ara-C treatment (100 mg/kg/day over 5 days).
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Neural Regen Res
Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease. [Abstract]2023 Aug;18(8):1818-1826. PMID: 36751811
Linagliptin purchased from MedChemExpress. Usage Cited in: Neural Regen Res. 2023 Aug;18(8):1818-1826. [Abstract]
Immunohistochemical staining for TH in the SNpc and STR. The MPTP group showed weaker staining for TH than the CON group, while the MPTP + EX-4 and MPTP + Linagliptin (LINA, 5 mg/kg; i.c. at the back of the neck; once daily for 14 days) groups showed stronger staining for TH than the MPTP group. Scale bar: 200 µm, 40 µm for low and high magnification, respectively.
Linagliptin purchased from MedChemExpress. Usage Cited in: Neural Regen Res. 2023 Aug;18(8):1818-1826. [Abstract]
Immunofluorescence staining for the M2 phenotype microglia marker CD206 (red, Cy3) in the SN. The intensity of the CD206 signal is weaker in the MPTP group and stronger in the MPTP + EX-4 and MPTP + Linagliptin (LINA, 5 mg/kg; i.c. at the back of the neck; once daily for 14 days) groups. Scale bar: 50 µm, 20 µm for low and high magnification, respectively. The results showed that the number of anti-inflammatory M2 microglia was clearly reduced in the SN of mice in the MPTP group, whereas the number of anti-inflammatory M2 microglia was increased in the exendin-4 and linagliptin treatment groups.
Linagliptin purchased from MedChemExpress. Usage Cited in: Neural Regen Res. 2023 Aug;18(8):1818-1826. [Abstract]
The effect of Linagliptin (1 nM-1 µM; 30 min) on SH-SY5Y cell viability, as assessed by CCK-8.
Linagliptin purchased from MedChemExpress. Usage Cited in: Neural Regen Res. 2023 Aug;18(8):1818-1826. [Abstract]
Apoptosis of SH-SY5Y cells was detected by flow cytometry. There was an increase in early apoptosis in the MPP (+) group, and a decrease in the MPP (+) + EX-4 (100 nM; 24 h) and MPP (+) (3 mM; 24 h) + Linagliptin (LINA, 100 nM; 24 h) groups.
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Talanta
Simultaneous enantiomeric separation of linagliptin and clopidogrel by capillary electrophoresis for the individual, combined, and enantiomeric ecotoxicity evaluation on Pseudokirchneriella subcapitata. [Abstract]2025 Mar 20:292:127992. PMID: 40132408 -
Biochem Pharmacol
Identification of a novel metabolite of vildagliptin in humans: Cysteine targets the nitrile moiety to form a thiazoline ring. [Abstract]2018 Oct:156:312-321. PMID: 30172711 -
Int J Mol Sci
Acute and Chronic Exposure to Linagliptin, a Selective Inhibitor of Dipeptidyl Peptidase-4 (DPP-4), Has an Effect on Dopamine, Serotonin and Noradrenaline Level in the Striatum and Hippocampus of Rats. [Abstract]2024 Mar 5;25(5):3008. PMID: 38474255 -
Molecules
Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal. [Abstract]2022 Apr 12;27(8):2478. PMID: 35458676 -
Neurochem Int
The role of linagliptin, a selective dipeptidyl peptidase-4 inhibitor, in the morphine rewarding effects in rats. [Abstract]2020 Feb;133:104616. PMID: 31809774 -
Sci Rep
The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. [Abstract]2017 Jun 28;7(1):4351. PMID: 28659588
Linagliptin purchased from MedChemExpress. Usage Cited in: Sci Rep. 2017 Jun 28;7(1):4351. [Abstract]
Western blot analysis of CREB protein phosphorylation in pancreas of KKAy mice treated with HBK001 and Linagliptin (2 mg/kg; p.o.).
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Toxicol Appl Pharmacol
Linagliptin ameliorates acetic acid-induced colitis via modulating AMPK/SIRT1/PGC-1α and JAK2/STAT3 signaling pathway in rats. [Abstract]2022 Mar 1:438:115906. PMID: 35122774 -
BMC Pharmacol Toxicol
Repurposing DPP-4 inhibitors as anticancer agents in KRAS-mutated pancreatic ductal adenocarcinoma. [Abstract]2025 Dec 8;26(1):208. PMID: 41361888 -
bioRxiv
Fatty Acid Transport Protein-2 (FATP2) Inhibition Enhances Glucose Tolerance through α-Cell-mediated GLP-1 Secretion. [Abstract]2025 Feb 6:2025.01.31.635976. PMID: 39975070 -
Solvent & Solubility
DMSO : 25 mg/mL (52.91 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.29 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.29 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 50% PEG300 50% Saline
Solubility: 5 mg/mL (10.58 mM); Clear solution; Need ultrasonic
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Each experimental group (vehicle or linagliptin treatment) consists of 10 individual ob/ob mice (n=10). Animals are treated orally once a day (8:00 AM) by gastrogavage using vehicle (1% methylcellulose) or linagliptin (3 mg/kg body weight in 1% methylcellulose) beginning 2 days (day−2) before wounding. After wounding, animals are subsequently treated once a day throughout the 10-day healing period.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (280 KB)
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SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
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Handling Instructions (2659 KB)
References
[1]. Eckhardt M, et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 d [Content Brief]
[2]. Thomas L, et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action [Content Brief]
[3]. Schurmann C, et al. The dipeptidyl peptidase-4 inhibitor linagliptin attenuates inflammation and accelerates epithelialization in wounds of diabetic ob/ob mice. J Pharmacol Exp Ther. 2012 Jul;342(1):71-80. [Content Brief]
[4]. Huan Y, et al. The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo. Sci Rep. 2017 Jun 28;7(1):4351. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.1162 mL | 10.5811 mL | 21.1622 mL | 52.9056 mL |
| 5 mM | 0.4232 mL | 2.1162 mL | 4.2324 mL | 10.5811 mL | |
| 10 mM | 0.2116 mL | 1.0581 mL | 2.1162 mL | 5.2906 mL | |
| 15 mM | 0.1411 mL | 0.7054 mL | 1.4108 mL | 3.5270 mL | |
| 20 mM | 0.1058 mL | 0.5291 mL | 1.0581 mL | 2.6453 mL | |
| 25 mM | 0.0846 mL | 0.4232 mL | 0.8465 mL | 2.1162 mL | |
| 30 mM | 0.0705 mL | 0.3527 mL | 0.7054 mL | 1.7635 mL | |
| 40 mM | 0.0529 mL | 0.2645 mL | 0.5291 mL | 1.3226 mL | |
| 50 mM | 0.0423 mL | 0.2116 mL | 0.4232 mL | 1.0581 mL |