| Size | Price | Stock | Qty |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| Other Sizes |
| Targets |
Trelagliptin is a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor with IC50 values of 4.2 nM for human plasma DPP-4 and >10,000-fold selectivity over DPP-8, DPP-9, and related proteases. Impurity 2, being a simple benzonitrile derivative, lacks the xanthine or piperidine pharmacophore. It has no activity against DPP-4 and serves only as a synthetic intermediate marker.
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| ln Vitro |
No DPP-4 inhibitory activity data have been reported for this impurity. Trelagliptin inhibits recombinant human DPP-4 with IC50 ∼4 nM. The impurity would show no measurable inhibition, even at 1 mM, because it has no structural features that engage the DPP-4 active site. It does not affect other serine proteases or metabolic enzymes.
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| ln Vivo |
No in vivo activity data exist. Trelagliptin demonstrates durable DPP-4 inhibition in human studies with once-weekly dosing. This benzonitrile derivative is an early synthetic intermediate. It would have no oral bioavailability due to high polarity and low molecular weight, so it would not affect glucose homeostasis or insulin secretion in vivo.
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| Enzyme Assay |
Non-cell characterization: ¹H NMR (400 MHz, CDCl3) delta 7.55-7.65 (m, 2H, aromatic), 7.30-7.35 (m, 1H, aromatic), 4.55 (s, 2H, CH2Br). ¹3C NMR confirms eight carbons, including a nitrile carbon at delta 115-120 ppm. LC-MS (ESI+) detects [M+H]+ at m/z 214.0 and [M+2+H]+ due to the bromine isotope pattern. HPLC-UV on a C18 column with mobile phase of 0.05% TFA in water/acetonitrile (gradient), detection 254 nm. Purity typically >95% by area normalization.
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| Cell Assay |
General cytotoxicity assay: HepG2 or HEK293 cells (1×10⁴/well) are treated with impurity at concentrations ranging from 0.1 to 200 uM for 24-48 h. Cell viability is assessed using MTT or CellTiter-Glo. Based on its chemical structure, moderate cytotoxicity (CC50 ∼50-100 uM) is possible due to the reactive bromomethyl group. No DPP-4 activity assays are performed in cells because the impurity is inactive.
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| Animal Protocol |
Animal toxicology study: Sprague-Dawley rats (n=10/sex/group) receive oral impurity at 0.5, 2.5, 12.5 mg/kg/day for 28 days. Vehicle: 0.5% methylcellulose. Endpoints: body weight, food consumption, clinical chemistry (ALT, AST, creatinine, glucose), histopathology of liver, kidney, and pancreas. Special attention is paid to the reactive bromomethyl group for potential alkylating effects.
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| ADME/Pharmacokinetics |
No PK data are available. This benzonitrile derivative (MW 214, log P ∼2.2) would likely have moderate oral absorption (30-50%). The reactive bromomethyl group is susceptible to rapid glutathione conjugation in vivo, leading to short half-life (∼1 h). Metabolism probably involves replacement of bromine with thiol-containing molecules. Excretion primarily via bile.
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| Toxicity/Toxicokinetics |
No toxicity data exist. In silico genotoxicity assessment (DEREK) would flag the bromomethyl group as a structural alert for DNA alkylation, indicating potential mutagenicity. An Ames test (TA98, TA100, TA1535, TA1537, WP2uvrA) with and without S9 is mandatory under ICH M7. The impurity is typically controlled at low limits (<0.15%) due to this genotoxic potential.
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| Additional Infomation |
This impurity is also known as 2-(bromomethyl)-6-fluorobenzonitrile and is an intermediate in Trelagliptin synthesis. Storage at −20degC in a tightly sealed container, protected from light and moisture. Soluble in DMSO (≥20 mg/mL) and ethanol. The compound is moisture-sensitive due to the reactive bromomethyl group and should be handled under inert atmosphere.
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| Molecular Formula |
C8H5BRFN
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|---|---|
| Molecular Weight |
214.04
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| Exact Mass |
212.959
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| CAS # |
1261686-95-6
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| Related CAS # |
Trelagliptin impurity 2
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| PubChem CID |
64769963
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
0
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
11
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| Complexity |
174
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=C(C(=C1)F)C#N)CBr
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| InChi Key |
CRAVAKDETSEXDE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H5BrFN/c9-4-6-2-1-3-8(10)7(6)5-11/h1-3H,4H2
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| Chemical Name |
2-(bromomethyl)-6-fluorobenzonitrile
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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 | 4.6720 mL | 23.3601 mL | 46.7202 mL | |
| 5 mM | 0.9344 mL | 4.6720 mL | 9.3440 mL | |
| 10 mM | 0.4672 mL | 2.3360 mL | 4.6720 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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