| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
Inolitazone (RS5444) increases the expression of p21 WAF1/CIP1, a cell cycle kinase inhibitor. When p21 WAF1/CIP1 is silenced, cells become resistant to inolitazone. Using a PPRE response element coupled to a luciferase reporter (PPRE3-tk-luc), a transient transfection test shows that inolitazone at a concentration of 10 nM activates PPARγ:RXRα-dependent transcription. The appropriate concentrations of Inolitazone, Rosiglitazone, or Troglitazone were applied to DRO cells in culture. PPRE3-tk-luc was transiently transfected into DRO cells in order to measure the effective concentration at which EC50 is reached. Inolitazone's EC50 is 1 nM, rosiglitazone's is 65 nM, and troglitazone's is 631 nM. Likewise, 0.8 nM for Inolitazone, 75 nM for Rosiglitazone, and 1412 nM for Troglitazone were determined to have the IC50 inhibitory values. PPARγ is selectively activated by inolitazone, but PPARα and PPARδ are not. After transient transfection with the relevant PPAR isoform (γ, α, or δ) and a PPAR response element connected to a luciferase reporter gene, a 10 nM Inolitazone alone was applied in the presence of PPARγ and PPRE3-tk-luc in a RIE rat intestinal cell line that does not express PPAR [1]. DRO cell proliferation is inhibited by 10 nM Inolitazone (RS5444) via a PPARγ-dependent mechanism [2].
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|---|---|
| ln Vivo |
Inolitazone (RS5444) coupled with paclitaxel demonstrated enhanced antiproliferative effect in cell culture and decreased ATC tumor development. When inolitazone was provided via the food to athymic nude mice prior to DRO tumor cell implantation, tumor growth was suppressed in a dose-response manner. At the highest dose, 0.025% Inolitazone decreased growth by 94.4% on day 32 compared to the control. In this therapy group, 5 of 10 mice did not develop overt tumors. On day 32, in the 0.0025% treatment group, tumor growth was decreased by 62.3% compared to the control, whereas the 0.00025% dose showed no growth inhibitory efficacy compared to the control. Tumors were allowed to build nests in mice, and mice were treated with 0.025% Inolitazone commencing 1 week following DRO or ARO tumor cell implantation. On day 35, Inolitazone-treated rats revealed 68.9% tumor growth inhibition in DRO tumors and 48.3% tumor growth inhibition in ARO tumors compared to their respective controls [1].
|
| References |
[1]. Copland JA, et al. Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene. 2006 Apr 13;25(16):2304-17.
[2]. Marlow LA, et al. Reactivation of suppressed RhoB is a critical step for the inhibition of anaplastic thyroid cancer growth. Cancer Res. 2009 Feb 15;69(4):1536-44 |
| Additional Infomation |
Efatutazone has been used in trials studying the treatment of Lymphoma, Liposarcoma, Solid Tumors, Multiple Myeloma, and Recurrent Thyroid Cancer, among others.
Efatutazone is an orally bioavailable thiazolidinedione and an agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma) with potential antineoplastic activity. Efatutazone binds to and activates PPAR-gamma thus inducing cell differentiation and apoptosis, leading to a reduction in cellular proliferation. PPAR-gamma is a nuclear hormone receptor and a ligand-activated transcription factor that controls the expression of genes involved in macromolecule metabolism and cell differentiation, specifically adipocyte differentiation. |
| Molecular Formula |
C27H26N4O4S
|
|---|---|
| Molecular Weight |
502.58
|
| Exact Mass |
502.167
|
| CAS # |
223132-37-4
|
| Related CAS # |
Inolitazone dihydrochloride;223132-38-5
|
| PubChem CID |
9832447
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.4±0.1 g/cm3
|
| Boiling Point |
794.6±60.0 °C at 760 mmHg
|
| Flash Point |
434.4±32.9 °C
|
| Vapour Pressure |
0.0±2.8 mmHg at 25°C
|
| Index of Refraction |
1.706
|
| LogP |
3.61
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
36
|
| Complexity |
782
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(N1)SC(CC2=CC=C(OCC3=NC4=CC=C(OC5=CC(C)=C(N)C(C)=C5)C=C4N3C)C=C2)C1=O
|
| InChi Key |
JCYNMRJCUYVDBC-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H26N4O4S/c1-15-10-20(11-16(2)25(15)28)35-19-8-9-21-22(13-19)31(3)24(29-21)14-34-18-6-4-17(5-7-18)12-23-26(32)30-27(33)36-23/h4-11,13,23H,12,14,28H2,1-3H3,(H,30,32,33)
|
| Chemical Name |
5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methylbenzimidazol-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione
|
| Synonyms |
RS5444 CS 7017 CS-7017, CS7017
|
| 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
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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 | 1.9897 mL | 9.9487 mL | 19.8973 mL | |
| 5 mM | 0.3979 mL | 1.9897 mL | 3.9795 mL | |
| 10 mM | 0.1990 mL | 0.9949 mL | 1.9897 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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