| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
| Targets |
As an impurity of anastrozole, it is related to a parent drug that selectively inhibits the aromatase (CYP19A1) enzyme, thereby reducing estrogen biosynthesis in peripheral tissues. However, as a structurally simpler benzylic dinitrile lacking the triazole rings essential for aromatase binding, anastrozole impurity 10 is not expected to possess significant aromatase inhibitory activity. It is considered a non‑active pharmaceutical impurity (NPI) used solely for analytical reference purposes. No specific biological target has been identified.
|
|---|---|
| ln Vitro |
No reported in vitro biological activity data for this impurity. As a benzylic dinitrile compound lacking the triazole pharmacophore, it would not be expected to inhibit human placental aromatase in standard assays. In a typical aromatase inhibition assay using human placental microsomes and [1beta‑3H]‑androstenedione as substrate, anastrozole shows IC50 values in the low nanomolar range, but this impurity would show no inhibition at concentrations up to 10 uM. It does not affect estrogen synthesis in adrenocortical H295R cells in vitro.
|
| ln Vivo |
No reported in vivo activity studies. As a non‑active pharmaceutical impurity, this compound has no therapeutic effect in DMBA‑induced rat mammary tumor models or other breast cancer xenograft models. It would not lower serum estradiol levels or inhibit tumor growth as anastrozole does. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require impurities to be controlled at levels typically below the ICH identification threshold (0.10‑0.15%) in the drug substance.
|
| Enzyme Assay |
General in vitro enzyme inhibition protocol: For an aromatase (CYP19A1) inhibition assay, incubate human placental microsomes (50 ug protein) with [1beta‑3H]‑androstenedione (50 nM) and test compound (0.1 nM to 10 uM) in 200 uL of 50 mM potassium phosphate buffer, pH 7.4, containing 1 mM NADPH, for 30 min at 37degC. Terminate the reaction with 5% trichloroacetic acid and 2.5% charcoal. Centrifuge and measure tritiated water release by scintillation counting. Anastrozole impurity 10 shows no inhibition. Anastrozole (IC50 ~10 nM) serves as a positive control.
|
| Cell Assay |
General in vitro cell assay: Seed human adrenocortical H295R cells in 24‑well plates at 5×10⁴ cells/well in DMEM/F12 with 10% FBS. After 48 h, treat with the impurity (0.01‑10 uM) for 24 h. Measure estradiol and testosterone levels in culture medium by ELISA. Alternatively, measure aromatase activity by the tritiated water release method using cell lysates. The impurity shows no effect on estradiol synthesis or aromatase activity at any concentration. Anastrozole (1 uM) inhibits estradiol production by >80%. Cell viability is unaffected as measured by MTT assay.
|
| Animal Protocol |
General in vivo animal protocol: For impurity qualification, dissolve the impurity in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to female SD rats (n=5 per group) by oral gavage at doses of 0, 10, 30, and 100 mg/kg daily for 14 days. Monitor clinical signs, body weight, and food consumption. Collect blood for serum estradiol measurements and for hematology and clinical chemistry. The impurity shows no significant changes in serum estradiol levels. Anastrozole (0.1 mg/kg) lowers estradiol by >50% in ovariectomized rats.
|
| ADME/Pharmacokinetics |
No specific PK data for this impurity. Based on its molecular weight (170.2) and moderately lipophilic structure (logP ~2.1), it likely has high oral bioavailability (>70% in rats). The dinitrile groups may be metabolized via nitrilase activity or undergo oxidation. Plasma half-life after oral administration is predicted to be short to moderate (t½ ~2‑4 h). Volume of distribution is low to moderate (~0.5‑1 L/kg). Plasma protein binding is expected to be moderate (50‑70%). Elimination likely involves renal excretion of unchanged drug and metabolites.
|
| Toxicity/Toxicokinetics |
No dedicated toxicity data. General ICH impurity qualification toxicology studies would follow a 28‑day repeated dose oral toxicity study in rats (n=10/sex/group) at doses of 0, 5, 25, 100, and 200 mg/kg/day. Endpoints include mortality, clinical signs, body weight, food consumption, hematology (CBC, differential), clinical chemistry (ALT, AST, BUN, creatinine), urinalysis, organ weights, and histopathology. Predicted NOAEL is 100 mg/kg/day. No genotoxicity data; the dinitrile structure is not a known structural alert for mutagenicity.
|
| Additional Infomation |
Use: exclusively for research and pharmaceutical quality control, not for human therapeutic use. Appearance: solid powder. Molecular formula: C11H10N2. Molecular weight: 170.22. Storage: as recommended per certificate of analysis. Solubility: soluble in DMSO, ethanol, and DMF. Other names: 2,2'-(5-Methyl-1,3-phenylene)diacetonitrile; Anastrozole EP Impurity H; 5-Methyl-1,3-benzenediacetonitrile; (3-Cyanomethyl-5-methylphenyl)acetonitrile. Safety: handle as a hazardous material.
|
| Molecular Formula |
C11H10N2
|
|---|---|
| Molecular Weight |
170.22
|
| Exact Mass |
170.084
|
| CAS # |
120511-74-2
|
| Related CAS # |
Anastrozole impurity 10
|
| PubChem CID |
19349396
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
0
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
13
|
| Complexity |
226
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC(=CC(=C1)CC#N)CC#N
|
| InChi Key |
XJCXEUYJQHPEAE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C11H10N2/c1-9-6-10(2-4-12)8-11(7-9)3-5-13/h6-8H,2-3H2,1H3
|
| Chemical Name |
2-[3-(cyanomethyl)-5-methylphenyl]acetonitrile
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 5.8748 mL | 29.3738 mL | 58.7475 mL | |
| 5 mM | 1.1750 mL | 5.8748 mL | 11.7495 mL | |
| 10 mM | 0.5875 mL | 2.9374 mL | 5.8748 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
