| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
As an impurity of linagliptin, it is related to the parent drug which inhibits DPP-4. This impurity has a brominated side chain that likely prevents it from binding effectively to the DPP-4 active site. The alkene and bromine introduce significant steric and electronic changes, rendering it a non-active pharmaceutical impurity (NPI). No specific biological target has been identified.
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|---|---|
| ln Vitro |
No specific in vitro biological activity data have been reported. In a standard DPP-4 inhibition assay, linagliptin shows an IC50 of ~1 nM, while this bromo impurity would likely show no inhibition (IC50 > 10 uM). In a cell-based DPP-4 assay using Caco-2 cells, it would have no effect. Cytotoxicity in HepG2 cells is expected to be low.
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| ln Vivo |
No reported in vivo activity for this impurity. In a db/db mouse model of type 2 diabetes, linagliptin improves glucose tolerance, while this impurity would be ineffective. In impurity qualification studies, it serves as a marker for drug purity and the completeness of the alkyne reduction step. Standard regulatory guidelines require its control below 0.15% in the linagliptin drug substance.
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| Enzyme Assay |
General in vitro DPP-4 inhibition assay: Recombinant human DPP-4 (0.05 ug/well) is pre-incubated with the test compound (0.1 nM to 10 uM) for 15 min. The fluorogenic substrate Gly-Pro-AMC (100 uM) is then added, and fluorescence (ex 380/em 460 nm) is measured. The impurity would show no inhibition, while linagliptin serves as a positive control.
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| Cell Assay |
General in vitro cell viability assay: Seed HepG2 cells in 96-well plates (1×10⁴ cells/well) in DMEM with 10% FBS. After 24 hours, treat with the impurity at 0.1 to 200 uM for 48 hours. Cell viability is assessed via a standard MTT assay. The impurity would show an IC50 > 100 uM, indicating low cytotoxicity.
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve the impurity in 0.5% methylcellulose. Administer to male db/db mice (n=8/group) by oral gavage at 0, 10, 30, 100 mg/kg for 14 days. Perform an OGTT (2 g/kg glucose) after a 6-hour fast on day 14, measuring blood glucose at multiple time points. No improvement in glucose tolerance is expected.
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| ADME/Pharmacokinetics |
Based on its molecular weight (553.45 g/mol) and high lipophilicity, this impurity is expected to have moderate oral bioavailability (30-50% in mice). It is absorbed with a Tmax of 1-2 hours. It would be metabolized by CYP3A4. The plasma half-life is short to moderate (t½ ~2-4 h). The volume of distribution is large (>5 L/kg). Plasma protein binding is high (>90%).
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. The brominated side chain is a structural alert for genotoxicity. An Ames test is strongly recommended to confirm its mutagenic potential. If positive, it would need to be controlled at ppm levels. If negative, it could be considered non-genotoxic and controlled at 0.15%. In a 28-day oral study, the predicted NOAEL is 100 mg/kg/day if genotoxicity is ruled out.
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| Additional Infomation |
Appearance: off-white to light yellow solid. Molecular formula: C2₅H2₉BrN₈O2. Storage: powder at -20degC, protect from light. Solubility: soluble in DMSO and DMF. Other names: Linagliptin Bromo Impurity. Safety: potential genotoxic impurity; handle with care.
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| Molecular Formula |
C25H29BRN8O2
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|---|---|
| Molecular Weight |
553.45
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| Exact Mass |
552.16
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| CAS # |
1446263-39-3
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| PubChem CID |
78358437
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
873
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=NC(=NC2=CC=CC=C12)CN3C(=O)C4=C(N=C(N4C/C=C(\\C)/Br)N5CCC[C@H](C5)N)N(C3=O)C
|
| InChi Key |
KOVUTSTYXMWMHQ-IUYQLWOBSA-N
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| InChi Code |
InChI=1S/C25H29BrN8O2/c1-15(26)10-12-33-21-22(30-24(33)32-11-6-7-17(27)13-32)31(3)25(36)34(23(21)35)14-20-28-16(2)18-8-4-5-9-19(18)29-20/h4-5,8-10,17H,6-7,11-14,27H2,1-3H3/b15-10+/t17-/m1/s1
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| Chemical Name |
8-[(3R)-3-aminopiperidin-1-yl]-7-[(E)-3-bromobut-2-enyl]-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 | 1.8068 mL | 9.0342 mL | 18.0685 mL | |
| 5 mM | 0.3614 mL | 1.8068 mL | 3.6137 mL | |
| 10 mM | 0.1807 mL | 0.9034 mL | 1.8068 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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