| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PPARgamma (Peroxisome Proliferator-Activated Receptor gamma). SR10221 is a non-covalent inverse agonist that binds to PPARgamma and represses its basal transcriptional activity.
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| ln Vitro |
In a cell-based reporter assay using RT112/84 FABP4-NLucP cells, SR10221 exhibits an IC₅0 of 1.6 nM as a PPARgamma inverse agonist. In biochemical peptide recruitment assays, SR10221 has an IC₅0 of 13 nM. SR10221 inhibits the growth of bladder cancer cell lines in vitro.
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| ln Vivo |
In vitro, SR10221 represses downstream PPARgamma target genes, leading to growth inhibition of bladder cancer cell lines. It exhibits antiproliferative activity in vitro, suggesting its potential as an anticancer agent. The compound is a non-covalent inverse agonist, meaning it reduces the constitutive transcriptional activity of PPARgamma.
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| Enzyme Assay |
A general cell-free protocol for PPARgamma inverse agonist binding: A fluorescence polarization (FP) competitive binding assay is used. Recombinant human PPARgamma ligand-binding domain (LBD) protein (GST-tagged, 5 nM) is incubated with a fluorescently labeled PPARgamma ligand (Fluormone PLM Red, 1 nM) in a buffer (100 mM potassium phosphate, pH 7.4, 100 ug/mL BSA, 0.01% NaN3) at room temperature for 2 hours. Varying concentrations of SR10221 (0.01 nM to 100 uM) are added to compete with the tracer. The FP signal is measured using a microplate reader with polarization filters. The IC₅0 is calculated, and the Kᵢ is derived using the Cheng-Prusoff equation. For the TR-FRET-based coactivator recruitment assay, LanthaScreen™ TR-FRET PPARgamma competitive binding assay kit is used. GST-tagged PPARgamma LBD is incubated with a terbium-labeled anti-GST antibody, a fluorescein-labeled SRC2-2 coactivator peptide, and varying concentrations of SR10221. The TR-FRET signal is measured, and the EC₅0 is calculated.
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| Cell Assay |
A general cellular protocol for PPARgamma inverse agonist activity using a reporter assay: RT112/84 bladder cancer cells stably transfected with the FABP4-NLucP reporter construct are seeded in 96-well white plates at 20,000 cells/well in phenol red-free RPMI 1640 medium containing 10% charcoal-stripped FBS. After 24 hours, the cells are treated with various concentrations of SR10221 (0.001 nM to 10 uM) for 18-24 hours. The medium is removed, and NanoLuc luciferase assay reagent is added. Luminescence is measured using a luminometer. The IC₅0 value is calculated by plotting the relative light units (RLU) against the log of the compound concentration. To assess cell viability, bladder cancer cell lines (e.g., RT112/84, T24, UM-UC-3) are seeded in 96-well plates and treated with SR10221 (0.1-10 uM) for 72 hours. Cell viability is measured using the MTT or CellTiter-Glo assay.
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| Animal Protocol |
General animal protocol for evaluating SR10221 in a bladder cancer xenograft model: Female nude mice (5-6 weeks old) are subcutaneously injected with 5×10⁶ RT112/84 bladder cancer cells in 0.1 mL of PBS mixed with Matrigel (1:1). When the average tumor volume reaches 100-150 mm3, the mice are randomized into treatment groups (n=8-10 per group). SR10221 is formulated in a suitable vehicle (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) and administered via oral gavage at doses of 10, 30, and 100 mg/kg once daily for 21 days. Tumor volume is measured twice weekly using a caliper, and body weight is recorded. At the end of the study, tumors are excised and weighed. Tumor tissues are processed for Western blot analysis to assess the expression of PPARgamma target genes (e.g., FABP4, CD36, ADRP) and for qRT-PCR to measure mRNA levels. Immunohistochemistry for Ki-67 and cleaved caspase-3 is performed to evaluate proliferation and apoptosis.
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| ADME/Pharmacokinetics |
General pharmacokinetic protocol for SR10221: Male Sprague-Dawley rats are administered SR10221 via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg) injection. The compound is formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline. Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose. Plasma concentrations of SR10221 are quantified by a validated LC-MS/MS method. Pharmacokinetic parameters, including Cmax, Tmax, AUC0₋ₜ, AUC0₋∞, terminal half-life (t½), clearance (CL), volume of distribution (Vd), and oral bioavailability (F%), are calculated using non-compartmental analysis. SR10221 has a molecular weight of 561.11, and it is soluble in DMSO at 100 mg/mL.
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| Toxicity/Toxicokinetics |
General toxicity protocol for SR10221: A 14-day repeated-dose oral toxicity study is performed in ICR mice. SR10221 is administered via oral gavage at doses of 30, 100, and 300 mg/kg/day. A vehicle control group is included. Clinical signs, body weight, and food consumption are monitored daily. At the end of the study, blood samples are collected for hematology (complete blood count with differential) and serum chemistry analysis (ALT, AST, ALP, BUN, creatinine, total protein, albumin, glucose). Gross necropsy is performed, and the weights of major organs (liver, kidney, spleen, heart, lung, brain, testes) are recorded. Histopathological examination of these organs is conducted. Bone marrow smears are prepared and examined for any signs of myelotoxicity. Special attention is given to the liver and adipose tissue due to the known role of PPARgamma in these tissues.
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| References | |
| Additional Infomation |
SR10221 has the molecular formula C33H3₇ClN2O4 and a molecular weight of 561.11. The IUPAC name is not provided. SR10221 is a non-covalent inverse agonist of PPARgamma. The compound is soluble in DMSO at 125 mg/mL (222.77 mM). For storage, the powder should be kept at -20degC for up to 3 years, and in solvent at -80degC for 6 months. The compound is typically shipped at room temperature and is stable for a few days during transit. SR10221 is a research tool for studying the role of PPARgamma in cancer, particularly in bladder cancer, and for developing novel therapeutic strategies targeting PPARgamma signaling.
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| Molecular Formula |
C33H37CLN2O4
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|---|---|
| Molecular Weight |
561.11
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| CAS # |
1415321-64-0
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| Appearance |
Solid powder
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| Density |
1.19±0.1 g/cm3(Predicted)
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| Boiling Point |
773.7±60.0 °C(Predicted)
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| LogP |
0
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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) |
DMSO : 125 mg/mL (222.77 mM; with sonication)
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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 | 1.7822 mL | 8.9109 mL | 17.8218 mL | |
| 5 mM | 0.3564 mL | 1.7822 mL | 3.5644 mL | |
| 10 mM | 0.1782 mL | 0.8911 mL | 1.7822 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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