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| 5mg |
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| Targets |
Linagliptin-d4 targets DPP-4, an enzyme responsible for the degradation of incretin hormones such as GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). Linagliptin is a highly potent and selective DPP-4 inhibitor with an IC₅₀ of 1 nM. By inhibiting DPP-4, Linagliptin increases the circulating levels of active GLP-1 and GIP, thereby enhancing glucose-dependent insulin secretion, suppressing glucagon release, and slowing gastric emptying. This mechanism improves glycemic control in patients with type 2 diabetes.
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| ln Vitro |
Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].
In vitro, Linagliptin demonstrates potent DPP-4 inhibition with an IC₅₀ of 1 nM. The compound shows high selectivity for DPP-4 over other DPP family members such as DPP-8 and DPP-9. Enzyme activity assays measure the cleavage of a chromogenic or fluorogenic substrate (e.g., Gly-Pro-pNA) by DPP-4 in the presence of varying concentrations of Linagliptin. The deuterated form, Linagliptin-d4, is used as an internal standard in cell-based and biochemical studies to accurately quantify Linagliptin concentrations. |
| ln Vivo |
Linagliptin-d4 is used in vivo as a deuterated internal standard for pharmacokinetic studies of Linagliptin. Linagliptin has demonstrated efficacy in improving glycemic control in diabetic animal models and is clinically approved (Tradjenta®) for the treatment of type 2 diabetes. In vivo, Linagliptin reduces blood glucose levels, HbA1c, and improves beta-cell function. The deuterated form is employed in LC-MS/MS methods to accurately quantify parent drug concentrations in plasma and tissues during preclinical and clinical pharmacokinetic studies.
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| Enzyme Assay |
In vitro enzyme assays for Linagliptin involve measuring DPP-4 activity using a fluorogenic substrate. The standard protocol includes incubating recombinant human DPP-4 with varying concentrations of Linagliptin (0.001-1000 nM) and a substrate such as Gly-Pro-AMC. Fluorescence is measured over time, and IC₅₀ values are calculated from dose-response curves. Selectivity assays against DPP-8 and DPP-9 are performed similarly. For the deuterated form, it is used as an internal standard in LC-MS-based assays to quantify Linagliptin concentrations.
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| Cell Assay |
Cell-based assays for Linagliptin are conducted in cell lines expressing DPP-4 or in primary human cells. Cells are treated with Linagliptin at concentrations ranging from 0.1-1000 nM. DPP-4 activity in cell lysates or culture supernatants is measured using fluorogenic substrates. GLP-1 levels in culture media are quantified by ELISA to assess the functional effect of DPP-4 inhibition. Cell viability is assessed to confirm lack of cytotoxicity. The deuterated analog is used as an internal standard for LC-MS/MS quantification of Linagliptin in cell lysates.
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| Animal Protocol |
In vivo animal experiments for Linagliptin typically use diabetic rodent models such as db/db mice or streptozotocin-induced diabetic rats. Animals are administered Linagliptin via oral gavage at doses of 0.1-10 mg/kg. Blood glucose levels are measured at various time points, and oral glucose tolerance tests (OGTT) are performed. Plasma samples are collected for analysis of active GLP-1 levels, insulin, and drug concentrations. The deuterated analog, Linagliptin-d4, is used as an internal standard in LC-MS/MS methods for the quantification of Linagliptin in these samples.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Linagliptin show good oral bioavailability and a long half-life (>100 hours) in humans, allowing once-daily dosing. The compound is primarily eliminated via bile and feces with minimal renal excretion. Linagliptin-d4 is used as an internal standard for PK studies. The deuterated form provides a mass shift of +4 Da relative to the non-deuterated compound. Storage: powder at -20°C for 3 years. Purity is typically >95%. Solubility and formulation details are as per standard protocols.
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| Toxicity/Toxicokinetics |
Linagliptin-d4 is supplied for research use only and is not intended for human administration. The non-deuterated parent compound, Linagliptin, is a clinically approved drug (Tradjenta®) for the treatment of type 2 diabetes. Common adverse effects include nasopharyngitis, hypoglycemia, and gastrointestinal symptoms. The deuterated form is used in trace quantities as an analytical standard. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
Linagliptin-d4 (CAS 2140263-92-7) is a stable isotope-labeled compound used as an internal standard for the quantification of Linagliptin. It is not intended for therapeutic use. Linagliptin is a clinically approved DPP-4 inhibitor (Tradjenta®) for the treatment of type 2 diabetes. The deuterium labeling is at the piperidine ring positions. The compound is a click chemistry reagent containing an alkyne group. It is for research and analytical applications only.
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| Molecular Formula |
C25H28N8O2
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|---|---|
| Molecular Weight |
476.57
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| Exact Mass |
476.258
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| CAS # |
2140263-92-7
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| Related CAS # |
Linagliptin;668270-12-0
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| PubChem CID |
119057561
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
1.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
35
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| Complexity |
885
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1(=O)C2N(C(N3C([2H])([2H])CC[C@@H](N)C3([2H])[2H])=NC=2N(C)C(N1CC1N=C(C)C2C(=CC=CC=2)N=1)=O)CC#CC
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| InChi Key |
LTXREWYXXSTFRX-JQABUVPCSA-N
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| InChi Code |
InChI=1S/C25H28N8O2/c1-4-5-13-32-21-22(29-24(32)31-12-8-9-17(26)14-31)30(3)25(35)33(23(21)34)15-20-27-16(2)18-10-6-7-11-19(18)28-20/h6-7,10-11,17H,8-9,12-15,26H2,1-3H3/t17-/m1/s1/i12D2,14D2
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| Chemical Name |
8-[(3R)-3-amino-2,2,6,6-tetradeuteriopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0983 mL | 10.4916 mL | 20.9833 mL | |
| 5 mM | 0.4197 mL | 2.0983 mL | 4.1967 mL | |
| 10 mM | 0.2098 mL | 1.0492 mL | 2.0983 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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