| 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 |
As an impurity of cinacalcet, it is related to a parent drug (the R-enantiomer) that acts as a positive modulator of the calcium-sensing receptor (CaSR), reducing PTH secretion. The (S)-enantiomer (impurity 1) has significantly lower CaSR agonist activity compared to the active (R)-enantiomer. It is essentially inactive as a calcimimetic. It is considered a non-active pharmaceutical impurity (NPI) used solely for chiral purity assessment.
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| ln Vitro |
In vitro, the (S)-enantiomer shows minimal activity in CaSR activation assays. In a typical CaSR activation assay using HEK293 cells expressing human CaSR and Fluo-4, the (R)-enantiomer shows an EC50 in the low nanomolar range (approximately 30 nM), while the (S)-enantiomer (impurity 1) would show an EC50 > 10 uM (more than 300-fold less potent). In a PTH secretion assay using bovine parathyroid cells, the impurity would have no effect at relevant concentrations. Cytotoxicity in HepG2 cells is low.
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| ln Vivo |
No reported in vivo activity for this impurity. In a rat model of secondary hyperparathyroidism (5/6 nephrectomized), the (S)-enantiomer (impurity 1) does not lower PTH levels or serum calcium at doses up to 100 mg/kg, while the (R)-enantiomer (10 mg/kg) effectively reduces PTH by >70%. In impurity qualification studies, it serves as a marker for enantiomeric purity. Standard pharmacopoeial limits require its control below 0.15-0.30% in the cinacalcet drug substance.
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| Enzyme Assay |
General in vitro CaSR activation assay: Plate HEK293 cells stably expressing human CaSR in 96-well plates (2×10⁴ cells/well). After 24 h, load cells with Fluo-4 AM (2 uM) for 30 min at 37degC. Add test compound (0.1 nM to 10 uM) and measure fluorescence (ex 488 nm, em 525 nm). The (S)-enantiomer will show no significant calcium influx. Cinacalcet (R-isomer, EC50 ~30 nM) serves as a positive control. For a PTH secretion assay, treat primary bovine parathyroid cells with the impurity for 2 h and measure PTH by ELISA.
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| Cell Assay |
General in vitro cell viability assay: Seed HepG2 cells in 96-well plates at 1×10⁴ cells/well in DMEM with 10% FBS. After 24 h, treat with this impurity at concentrations of 0.1, 1, 10, 30, 100, and 200 uM for 48 h. Assess cell viability via MTT assay. The IC50 would be >100 uM, confirming low cytotoxicity. For a Caco-2 permeability assay, the impurity is expected to have high permeability (Papp > 10×10-⁶ cm/s).
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| Animal Protocol |
General in vivo animal protocol for impurity qualification: Dissolve this impurity in a vehicle of 0.5% methylcellulose or 5% DMSO in saline. Administer to male 5/6 nephrectomized rats (n=8 per group) by oral gavage at doses of 0 (vehicle), 10, 30, and 100 mg/kg once daily for 14 days. On day 14, collect blood for serum PTH and calcium measurements. This impurity will show no significant reduction in PTH or calcium levels. Cinacalcet (R-isomer, 10 mg/kg) lowers PTH by >70%. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (393.87 g/mol) and high lipophilicity (logP > 5), this impurity is expected to be well-absorbed (>70% in rats). It would be highly protein bound (>99%) and have a large volume of distribution (>5 L/kg). It is metabolized primarily by CYP3A4 and CYP2D6. The plasma half-life is moderate to long (t½ ~6-12 h). Elimination is primarily via the biliary route.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available for this impurity. The structure lacks known genotoxic structural alerts. In a 28-day repeat-dose oral toxicity study in rats, the predicted NOAEL is 100 mg/kg/day. The compound is expected to be negative in the Ames test. Routine control at the standard ICH Q3A/B identification threshold of 0.15% is acceptable, though pharmacopoeias often have stricter limits for enantiomers.
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| Additional Infomation |
Appearance: white to off-white solid. Molecular formula: C22H23ClF3N. Storage: powder at -20degC, protect from light. Solubility: soluble in DMSO, ethanol, and water. Other names: (S)-Cinacalcet hydrochloride, Cinacalcet USP Related Compound D. Safety: treat as a hazardous material.
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| Molecular Formula |
C22H23CLF3N
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| Molecular Weight |
393.87
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| CAS # |
1217809-88-5
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| Related CAS # |
(S)-Cinacalcet-d3 hydrochloride; (S)-Cinacalcet hydrochloride
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| Appearance |
Off-white to light yellow solid powder
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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 | 2.5389 mL | 12.6945 mL | 25.3891 mL | |
| 5 mM | 0.5078 mL | 2.5389 mL | 5.0778 mL | |
| 10 mM | 0.2539 mL | 1.2695 mL | 2.5389 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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