GSK'547

Catalog No.S8787 Batch:S878701

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Technical Data

Formula

C20H18F2N6O
Molecular Weight 396.39 CAS No. 2226735-55-1
Solubility (25°C)* In vitro DMSO 29 mg/mL (73.16 mM)
Water Insoluble
Ethanol 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.)

Preparing Stock Solutions

Biological Activity

Description GSK'547 is a highly selective and potent inhibitor of RIP1 (RIPK1) exhibiting a 400-fold improvement in mouse pharmacokinetic oral exposure compared with GSK'963
Targets
RIP1 [1]
In vitro

GSK'547 (RIP1i) treatment in vitro directs the programming of bone marrow-derived macrophages (BMDM) toward an immunogenic phenotype, upregulating MHC-II, TNFa, and IFNg, while concomitantly reducing CD206, IL-10, and TGFb expression. Moreover, RIP1i upregulates STAT1 signaling in BMDM, which is associated with M1 programming, but reduced STAT3, STAT5, and STAT6 signaling, which are linked to M2-like macrophage differentiation. Furthermore, RIP1i-treated macrophages display enhanced ability to capture antigen[1].
In vivo

Administration of GSK'547 (RIP1i) in mouse chow achieves in vivo steady-state concentrations above the L929 IC90 over a 24-hr period. High serum concentrations of RIP1i are sustained over a 6-week treatment course. RIP1i treatment is well tolerated without evident pathology. In mice challenged with orthotopic PDA (pancreatic ductal adenocarcinoma) tumor cells derived from KPC mice, RIP1i reduces tumor burden and extends survival cpmpared with mice treated with controls or Nec-1s. RIP1i also protects against established tumors and liver metastases[1].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    L929 cells

  • Concentrations

    --

  • Incubation Time

    30 min

  • Method

    Cells are pretreated with RIP1i at various doses for 30 min. Induced cell death is evaluated 24 hr later by measuring cellular ATP levels.
Animal Study:

[1]
  • Animal Models

    C57BL/6 mice

  • Dosages

    100 mg/kg/day

  • Administration

    oral

Selleck's GSK'547 has been cited by 1 publication

Z-DNA binding protein 1 mediates necroptotic and apoptotic cell death pathways in murine astrocytes following herpes simplex virus-1 infection [ J Neuroinflammation, 2022, 19(1):109] PubMed: 35549723

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.