| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
IC50: 0.3 μM (ASH); 1.3 μM (GR-dependent luciferase expression); 0.7 μM (AR-dependent luciferase expression)[1]
SEW84 targets the Aha1-stimulated Hsp90 (ASH) ATPase activity. Hsp90 is a molecular chaperone involved in the folding, stabilization, and activation of client proteins, many of which are involved in cell signaling and cancer. Aha1 is a co-chaperone that stimulates Hsp90 ATPase activity, and SEW84 specifically inhibits this stimulated activity. |
|---|---|
| ln Vitro |
SEW84 (5 μM) completely inhibits ASH activity with an IC50 value of 0.3 μM[1]. GR- and AR-dependent luciferase expression was suppressed by SEW84, with IC50 values of 1.3 and 0.7 μM, respectively[1]. The Hsp90-Dependent folding of firefly luciferase is inhibited by SEW84 (0–20 μM)[1]. Particularly, phosphorylated tau is cleared by SEW84 (0, 3, 10, 30 μM; 24 h)[1].
In vitro, SEW84 inhibits Aha1-stimulated Hsp90 ATPase activity with an IC₅0 of 0.3 microM. The compound is used to study the role of Hsp90 in protein folding and the regulation of client protein activity. It serves as a tool to dissect the contributions of Aha1 to Hsp90 function. |
| ln Vivo |
In vivo, SEW84 may be used to study the effects of inhibiting Aha1-stimulated Hsp90 activity on protein deposition diseases. Inhibition of Hsp90 has been shown to promote the degradation of misfolded proteins and may have therapeutic potential in neurodegenerative diseases and cancer.
|
| Enzyme Assay |
Enzyme assays for SEW84 typically measure Hsp90 ATPase activity in the presence of Aha1. The assay uses purified Hsp90 and Aha1 proteins, and ATP hydrolysis is quantified by measuring inorganic phosphate release or using coupled enzyme assays. IC₅0 values are calculated from dose-response curves.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: tau-0N4R-HeLa cells Tested Concentrations: 0, 3, 10, 30 μM Incubation Duration: 24 h Experimental Results: decreased the expression of phospho-Tau. Immunofluorescence[1] Cell Types: RFP-tau-0N4R HEK cells Tested Concentrations: 1, 10 μM Incubation Duration: 24 h Experimental Results: Completely abrogated the aggregation of tau. Cell Proliferation Assay[1] Cell Types: LNCaP and 22Rv1 cells Tested Concentrations: 0 -100 μM Incubation Duration: 24 h Experimental Results: Observed a synergistic decrease in LNcaP cell proliferation when combined 1 μM GA with 10 μM SEw84. Cellular assays for SEW84 may involve treating cells with the compound and assessing Hsp90 client protein levels and activity. Client proteins such as HER2, Akt, and Raf-1 are monitored by Western blot. Cell viability and proliferation assays can also be performed to assess functional consequences. |
| Animal Protocol |
In vivo studies with SEW84 are likely conducted in rodent models of protein deposition diseases or cancer. The compound is typically administered via intraperitoneal or oral administration. Disease progression, protein aggregation, and tissue pathology are assessed.
|
| ADME/Pharmacokinetics |
Pharmacokinetic data for SEW84 are limited. As a small molecule with a molecular weight of 422.40, it may have reasonable oral bioavailability. Standard pharmacokinetic studies would involve measuring plasma concentrations after administration and calculating parameters such as half-life, Cmax, and AUC.
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| Toxicity/Toxicokinetics |
Toxicity data for SEW84 are limited. Hsp90 inhibitors can have significant toxicity due to the broad range of client proteins affected. Standard safety precautions for laboratory handling of research compounds should be followed.
|
| References | |
| Additional Infomation |
SEW84 is a research-use compound and is not approved for therapeutic applications. It is also known as SEW04784. The compound is used to study the Hsp90 chaperone system and its role in protein folding and disease. It is available from multiple research suppliers.
|
| Molecular Formula |
C19H14F4N4OS
|
|---|---|
| Molecular Weight |
422.399276256561
|
| Exact Mass |
422.082
|
| CAS # |
259089-67-3
|
| PubChem CID |
2740977
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
4.4
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
29
|
| Complexity |
583
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=CC(=C1)NC(=S)NNC(=O)C2=CC=CN2C3=CC=C(C=C3)F)C(F)(F)F
|
| InChi Key |
QEJONNSHVNSZBJ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H14F4N4OS/c20-13-6-8-15(9-7-13)27-10-2-5-16(27)17(28)25-26-18(29)24-14-4-1-3-12(11-14)19(21,22)23/h1-11H,(H,25,28)(H2,24,26,29)
|
| Chemical Name |
1-[[1-(4-fluorophenyl)pyrrole-2-carbonyl]amino]-3-[3-(trifluoromethyl)phenyl]thiourea
|
| 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)
|
| 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 | 2.3674 mL | 11.8371 mL | 23.6742 mL | |
| 5 mM | 0.4735 mL | 2.3674 mL | 4.7348 mL | |
| 10 mM | 0.2367 mL | 1.1837 mL | 2.3674 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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