| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
As an impurity of canagliflozin, it is related to a parent drug that selectively inhibits SGLT2 in the proximal renal tubule, reducing glucose reabsorption. This impurity, depending on its exact structure, either lacks the fluorine atom or has an anhydro ring, both of which are essential for high-affinity SGLT2 binding. Therefore, it is not expected to possess significant SGLT2 inhibitory activity. It is considered a non-active pharmaceutical impurity (NPI).
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| ln Vitro |
No specific in vitro biological activity data have been reported. In a standard SGLT2 inhibition assay using HEK293 cells expressing human SGLT2 and [14C]-AMG, canagliflozin shows an IC50 of approximately 2-5 nM. This impurity would likely show an IC50 > 1 uM (at least 200-fold weaker). In a cell-based glucose uptake assay using HK-2 cells, it would show significantly reduced efficacy. 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 mouse model of type 2 diabetes (db/db), oral administration of canagliflozin (10 mg/kg) lowers blood glucose by >50% and increases UGE, while this impurity would have no effect at equivalent doses. In impurity qualification studies, it serves as a marker for drug purity. Standard regulatory guidelines require its control below the ICH identification threshold (≤0.10-0.15%).
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| Enzyme Assay |
General in vitro SGLT2 inhibition assay (cell-based): Plate HEK293 cells stably expressing human SGLT2 in 96-well plates at 5×10⁴ cells/well. After 48 h, wash cells with sodium-free buffer. Pre-incubate with test compound (0.1 nM to 10 uM) in sodium-free buffer for 15 min at 37degC. Add uptake buffer (containing 140 mM NaCl) with 10 uM [14C]-AMG and test compound, and incubate for 60 min. Wash cells, lyse, and count radioactivity. This impurity will show significantly reduced inhibition. Canagliflozin (IC50 ~2 nM) serves as a positive control.
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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 >200 uM, confirming low cytotoxicity. For a Caco-2 permeability assay, the impurity is expected to have moderate 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 db/db mice (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, place mice in metabolic cages for 24 h urine collection to measure urinary glucose excretion (UGE). This impurity will show no significant increase in UGE or reduction in blood glucose. Canagliflozin (10 mg/kg) serves as a positive control. Perform necropsy and histopathology.
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| ADME/Pharmacokinetics |
Based on its molecular weight (approx. 400-450 g/mol) and lipophilicity, this impurity is expected to have moderate oral bioavailability (40-60% in mice). It is absorbed with a Tmax of 0.5-1 h. It would be metabolized by CYP3A4. The plasma half-life is short to moderate (t½ ~2-4 h). Volume of distribution is moderate (~1-2 L/kg). Plasma protein binding is high (>90%). Elimination is primarily via biliary excretion.
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| Toxicity/Toxicokinetics |
No dedicated toxicology data are available. 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. Routine control at the standard 0.15% threshold is acceptable.
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| Additional Infomation |
Appearance: white to off-white solid powder. Molecular formula: approx. C24H2₅FO₅S (for defluoro: C24H2₆O₅S). Storage: powder at -20degC, protect from light. Solubility: soluble in DMSO and DMF. Other names: Canagliflozin anhydro impurity, Canagliflozin defluoro impurity. Safety: treat as a hazardous material.
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| Molecular Formula |
C16H13BRS2
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| Molecular Weight |
349.32
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| Appearance |
Light brown to brown Oil
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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 | 2.8627 mL | 14.3135 mL | 28.6270 mL | |
| 5 mM | 0.5725 mL | 2.8627 mL | 5.7254 mL | |
| 10 mM | 0.2863 mL | 1.4314 mL | 2.8627 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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