SH-4-54

Catalog No.S7337 Batch:S733701

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Technical Data

Formula

C29H27F5N2O5S 
Molecular Weight 610.59 CAS No. 1456632-40-8
Solubility (25°C)* In vitro DMSO 100 mg/mL (163.77 mM)
Ethanol 79 mg/mL (129.38 mM)
Water Insoluble
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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]
(Cell-free assay)		 STAT5 [1]
(Cell-free assay)
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]

Protocol (from 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:

[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

  • Dosages

    Suspended in 50% polyethylene glycol 300 in water

  • Administration

    i.p.

Customer Product Validation

Data from [Data independently produced by , , Diabetologia, 2015, 58: 2064–2073]

Data from [Data independently produced by , , Sci Rep, 2016, 6:33358.]

Data from [Data independently produced by , , Biochim Biophys Acta, 2015, 1852(12):2671-7]

Data from [Data independently produced by , , J Infect, 2016, 72(3):338-52.]

Selleck's SH-4-54 has been cited by 64 publications

BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion [ Nat Commun, 2024, 15(1):1835] PubMed: 38418488
Blocking the MIR155HG/miR-155 axis reduces CTGF-induced inflammatory cytokine production and α-SMA expression via upregulating AZGP1 in hypertrophic scar fibroblasts [ Cell Signal, 2024, S0898-6568(24)00170-0] PubMed: 38729323
JAK3/STAT5 signaling-triggered upregulation of PIK3CD contributes to gastric carcinoma development [ J Cell Commun Signal, 2024, 18(1):e12017] PubMed: 38545256
JAK-STAT Signaling in Inflammatory Breast Cancer Enables Chemotherapy-Resistant Cell States [ Cancer Res, 2023, 83(2):264-284] PubMed: 36409824
Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans [ JCI Insight, 2023, 8(22)e164672] PubMed: 37856221
CRISPR/Cas9-engineering of HMC-1.2 cells renders a human mast cell line with a single D816V-KIT mutation: An improved preclinical model for research on mastocytosis [ Front Immunol, 2023, 14:1078958] PubMed: 37025992
Single-cell transcriptome profiling of the immune space-time landscape reveals dendritic cell regulatory program in polymicrobial sepsis [ Theranostics, 2022, 12(10):4606-4628] PubMed: 35832091
Blockade of STAT3/IL-4 overcomes EGFR T790M-cis-L792F-induced resistance to osimertinib via suppressing M2 macrophages polarization [ EBioMedicine, 2022, 83:104200] PubMed: 35932642
BCL6 inhibition ameliorates ruxolitinib resistance in CRLF2-rearranged acute lymphoblastic leukemia [ Haematologica, 2022, 10.3324/haematol.2022.280879] PubMed: 36005560
UHMK1 aids colorectal cancer cell proliferation and chemoresistance through augmenting IL-6/STAT3 signaling [ Cell Death Dis, 2022, 13(5):424] PubMed: 35501324

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