SH-4-54 STAT inhibitor

Jump to

Quality Control

Batch: Purity: 99.96%

99.96

Related Targets	EGFR JAK Pim
Other STAT Inhibitors	Napabucasin (BBI608) Stattic NSC 74859 (S3I-201) Cryptotanshinone (Tanshinone C) C188-9 (TTI-101) BP-1-102 AS1517499 Nifuroxazide HO-3867 Homoharringtonine (HHT)

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
127EF	Cytotoxicity assay		3 days	Cytotoxicity against human 127EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.066μM.	24900612
30M	Cytotoxicity assay		3 days	Cytotoxicity against human 30M cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.1μM.	24900612
84EF	Cytotoxicity assay		3 days	Cytotoxicity against human 84EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.102μM.	24900612
67EF	Cytotoxicity assay		3 days	Cytotoxicity against human 67EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.106μM.	24900612
73EF	Cytotoxicity assay		3 days	Cytotoxicity against human 73EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.162μM.	24900612
25EF	Cytotoxicity assay		3 days	Cytotoxicity against human 25EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.234μM.	24900612
30M	Cytotoxicity assay		8 days	Cytotoxicity against human 30M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=0.43μM.	24900612
73M	Cytotoxicity assay		8 days	Cytotoxicity against human 73M cells assessed as cell viability after 8 days by Alamar Blue assay, IC50=1.03μM.	24900612
147EF	Apoptosis assay	0.1 to 1 uM	3 hrs	Induction of apoptosis in human 147EF cells assessed as PARP cleavage at 0.1 to 1 uM after 3 hrs by Western blotting analysis	24900612
147EF	Function assay	0.1 to 1 uM	3 hrs	Inhibition of AKT phosphorylation in human 147EF cells at 0.1 to 1 uM after 3 hrs by Western blotting analysis	24900612
147EF	Function assay	0.1 to 1 uM	3 hrs	Inhibition of STAT3 phosphorylation at Y705 in human 147EF cells at 0.1 to 1 uM after 3 hrs by Western blotting analysis	24900612
73M	Function assay	1 uM		Inhibition of STAT3 phosphorylation at Y705 in human 73M cells at 1 uM	24900612
147EF	Function assay		2 to 72 hrs	Inhibition of STAT3 in human 147EF cells assessed as reduction of phosphorylated Bcl-xL level after 2 to 72 hrs by Western blotting analysis	24900612
147EF	Function assay		2 to 72 hrs	Inhibition of STAT3 in human 147EF cells assessed as reduction of phosphorylated cyclin D1 level after 2 to 72 hrs by Western blotting analysis	24900612
BT73	Function assay	10 mg/kg	3 days	In vivo inhibition of STAT3 phosphorylation in tumor of NOD-SCID mouse xenografted with human BT73 cells at 10 mg/kg, ip administered as 4 days on/3 days off schedule measured 2 hrs post last dose	24900612
BT73	Antitumor assay	10 mg/kg	3 days	Antitumor activity against human BT73 cells xenografted in NOD-SCID mouse assessed as decrease in tumor size at 10 mg/kg, ip administered as 4 days on/3 days off schedule measured 2 hrs post last dose by hematoxylin/eosin staining	24900612
BT73	Antitumor assay	10 mg/kg	3 days	Antitumor activity against human BT73 cells xenografted in NOD-SCID mouse assessed as induction of apoptosis in tumor at 10 mg/kg, ip administered as 4 days on/3 days off schedule measured 2 hrs post last dose by TUNEL assay	24900612
BT73	Antitumor assay	10 mg/kg	3 days	Antitumor activity against human BT73 cells xenografted in NOD-SCID mouse assessed as tumor growth inhibition by measuring downregulation of Ki67 protein expression at 10 mg/kg, ip administered as 4 days on/3 days off schedule measured 2 hrs post last dos	24900612
Vero	Function assay			Vero cells viability counterscreen for qRT-PCR qHTS assay of selected Zika virus inhibitors	33229545
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	610.59	Formula	C₂₉H₂₇F₅N₂O₅S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1456632-40-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CN(CC(=O)N(CC1=CC=C(C=C1)C2CCCCC2)C3=CC=C(C=C3)C(=O)O)S(=O)(=O)C4=C(C(=C(C(=C4F)F)F)F)F

Solubility

In vitro
Batch:

DMSO : 100 mg/mL (163.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	STAT3 (Cell-free assay) 300 nM(Kd) STAT5 (Cell-free assay) 464 nM(Kd)
In vitro	SH-4-54 shows unprecedented cytotoxicity in human glioblastoma brain cancer stem cells (BTSCs), while it has no toxicity in human fetal astrocytes. In addition, this compound effectively suppresses STAT3 phosphorylation and its downstream transcriptional targets.
Kinase Assay	Surface Plasmon Resonance (SPR) studies
Kinase Assay	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.
In vivo	In mice orthotopically xenografted with BT73, SH-4-54 (10 mg/kg i.p.) exhibits BBB permeability, potently suppresses glioma tumour growth, and inhibits pSTAT3.
References	[1] https://pubmed.ncbi.nlm.nih.gov/24900612/

Applications

Methods	Biomarkers	Images	PMID
Western blot	LMP1 / p-STAT3 / STAT3		28445949

Tech Support

Handling Instructions

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

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Chemical Structure

Molecular Weight: 610.59