SH-4-54 Chemical Structure

SH-4-54 Chemical Structure
Molecular Weight: 610.59

Validation & Quality Control

2 customer reviews :

Quality Control & MSDS

Product Information

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  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description SH-4-54 is a potent STAT inhibitor with KD of 300 nM and 464 nM for STAT3 and STAT5, respectively.
Targets STAT3 [1] STAT5 [1]
IC50 300 nM(Kd) 464 nM(Kd)
In vitro SH-4-54 shows unprecedented cytotoxicity in human glioblastoma brain cancer stem cells (BTSCs), while has no toxicity in human fetal astrocytes. In addition, SH-4-54 effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets. [1]
In vivo In mice orthotopically xenografted with BT73, SH-4-54 (10 mg/kg i.p.) exhibits BBB permeability, potently suppresses glioma tumor growth, and inhibits pSTAT3. [1]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

Surface Plasmon Resonance (SPR) studies The binding experiments are carried out on a ProteOn XPR36 biosensor at 25°C using the HTE sensor chip. The flow cells of the sensor chip are loaded with a nickel solution at 30 μL/min for 120 s to saturate the Tris–NTA surface with Ni(II) ions. Purified His-tagged STAT3 and STAT5 in PBST buffer (PBS with 0.005% (v/v) Tween-20 and 0.001% DMSO pH 7.4) is injected in the first and second channels of the chip respectively in the vertical direction at a flow rate of 25 μg/μL for 300 s, which attained, on average, ~8000 resonance unit (RU). After a wash with PBST buffer, inhibitors binding to the immobilized proteins is monitored by injecting a range of concentrations along with a blank at a flow rate of 100 μL/min for 200 s for each of these small molecules. When the injection of the small molecule inhibitor is completed, running buffer is allowed to flow over the immobilized substrates for the non-specifically bound inhibitors to dissociate for 600 s. Following dissociation of the inhibitors, the chip surface is regenerated with an injection of 1 M NaCl at a flow rate of 100 μL/ml for 18 s. Interspot channel reference is used for non-specific binding corrections and the blank channel used with each analyte injection served as a double reference to correct for possible baseline drift. Data are analyzed using ProteOn Manager Software version 3.1. The Langmuir 1:1 binding model was used to determine the KD values.

Cell Assay: sup>[1]

Cell lines BTSC lines 25M, 67EF, 73EF, 84EF and 127EF
Concentrations ~25 μM
Incubation Time 72 hours
Method BTSC spheres are dissociated to single cells with the enzyme Accumax, seeded at 1500 cells/ 96-well and treated with drug or vehicle (DMSO) one day after plating. Cytotoxicity studies are repeated independently using BTSC lines 25M, 67EF, 73EF, 84EF and 127EF. BTSC spheres are dissociated to single cells as above and plated in 96 well plates in triplicate at 3000 cells/ 96-well. In both sets of experiments drugs are used as serial dilutions within the range of 5 μM to 100 nM in the first set and 25 μM to 10 nM. Cell viability following drug treatment is assessed three days later using the alamarBlue assay according to the manufacturer’s instructions. All culture experiments are performed in triplicate with a minimum of three wells per condition.

Animal Study: [1]

Animal Models NOD-SCID bearing ed with BT73 glioma xenografts
Formulation 10 mg/kg
Dosages Suspended in 50% polyethylene glycol 300 in water
Administration i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Haftchenary S, et al. ACS Med Chem Lett. 2013, 4(11), 1102-1107.

Chemical Information

Download SH-4-54 SDF
Molecular Weight (MW) 610.59
Formula

C29H27F5N2O5

CAS No. 1456632-40-8
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 100 mg/mL (163.77 mM)
Ethanol 50 mg/mL warming (81.88 mM)
Water <1 mg/mL (<1 mM)
In vivo
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 4-[[(4-cyclohexylphenyl)methyl][2-[methyl[(2,3,4,5,6-pentafluorophenyl)sulfonyl]amino]acetyl]amino]-benzoic acid

Customer Product Validation(2)


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Rating
Source Diabetologia, 2015, 58: 2064–2073. SH-4-54 purchased from Selleck
Method Western Blot
Cell Lines PRL-stimulated INS-1 cells
Concentrations 25 µM
Incubation Time 72 h
Results Specific inhibitor of STAT5 pathway significantly decreased the protein levels of FOXM1 and survivin in PRL-stimulated INS-1 cells.

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Rating
Source Biochim Biophys Acta, 2015, 1852(12):2671-7. SH-4-54 purchased from Selleck
Method qRT-PCR
Cell Lines Pancreatic acini
Concentrations 10 µM
Incubation Time 45 min
Results The acinar CCL2 mRNA up-regulation induced by OA or LA was significantly (p<0.01) reduced by pre-treatment with the NF-κB inhibitor JSH-23 as well as with the STAT3 inhibitor SH-4-54.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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