Entospletinib (GS-9973)

Catalog No.S7523 Batch:S752304

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Technical Data

Formula

C23H21N7O
Molecular Weight 411.46 CAS No. 1229208-44-9
Solubility (25°C)* In vitro DMSO 27 mg/mL (65.61 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
4%DMSO 30%PEG300 5%Tween80 61%ddH2O
2.5mg/ml Taking the 1 mL working solution as an example, add 40 μL of clarified DMSO stock solution of 62.5 mg/ml to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 610 μL of ddH2O to make it clear. Volume up to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM in a cell-free assay and showed 13- to >1000-fold cellular selectivity for Syk over other kinases(including Jak2, ckit, Flt3, Ret, KDR) as assessed by target protein phosphorylation or functional response.
Targets
Syk [1]
(Cell-free assay)
7.7 nM
In vitro

GS-9973 shows good bidirectional permeability across Caco-2 cell monolayers in vitro. In cells, GS-9973 also shows excellent selectivity for Syk, and potently inhibits BCR-mediated activation and proliferation of B-cells as well as immune-complex-stimulated cytokine production in monocytes. [1] The combination of GS-9973 synergistically inhibits CLL cell viability and further disrupts chemokine signaling. [2]
In vivo

GS-9973 (1 mg/kg p.o.) shows moderate to high bioavailability in rat and dog. In a rat collagen-induced arthritis model, GS-9973 (1-10 mg/kg p.o.) significantly inhibits ankle inflammation. Moreover, GS-9973 also shows disease-modifying activity in multiple histological measurements, including inhibition of pannus formation, cartilage damage, bone resorption, and peritosteal bone formation with ED50 ranging from 1.2 to 3.9 mg/kg . [1]
Features Orally bioavailable Syk-selective inhibitor that has been tested in Phase II clinical trials for treatment of Haematological Malignancies.

Protocol (from reference)

Kinase Assay:

[1]
  • Kinase Assays

    Full-length baculovirus-expressed Syk kinase activity is measured in a Lance-based assay format in a final volume of 25 μL containing 25 mM Tris–HCl, pH 7.5, 5 mM β-glycerophosphate, 2 mM DTT, 0.1 mM Na3VO4, 10 mM MgCl2, 0.5 μM Promega PTK biotinylated peptide substrate 1, 0.01% casein, 0.01% Triton X-100, and 40 mM ATP (Km for ATP) incubated at room temperature for 60 min. Reactions are stopped with the addition of 30 mM EDTA containing 30 μL of SA-APC and 4 nM PT-66 antibody and the plates measured on a Perkin-Elmer Envision. IC50 values for test compounds are determined using a four-parameter linear regression algorithm.
Cell Assay:

[1]
  • Cell lines

    MV-4-11 cells

  • Concentrations

    ~10 μM

  • Incubation Time

    72 hours

  • Method

    Functional impact on cellular Flt3 activity is determined by measuring compound inhibition of MV-4-11 cell proliferation. A total of 104 cells are diluted in RPMI medium containing 10% FBS in 96-well flat-bottomed tissue culture plates and incubated with compound dilutions for 72 h at 37 癈. Alamar blue (10%) is added to the cells, which were incubated for an additional 12-18 h at 37 癈, and inhibition of the relative cell numbers is determined by spectrophotometer readings at 570/600 nm.
Animal Study:

[1]
  • Animal Models

    Rat Collagen-Induced Arthritis (CIA) Model

  • Dosages

    ~10 mg/kg bid

  • Administration

    p.o.

Customer Product Validation

Data from [Data independently produced by , , Blood, 2016, 127(25):3192-201]

Data from [Data independently produced by , , J Hematol Oncol, 2018, 11(1):23]

Data from [Data independently produced by , , Biochim Biophys Acta, 2017, 1864(4):687-696]

Data from [Data independently produced by , , J Immunol, 2016, 197(5):1587-96.]

Selleck's Entospletinib (GS-9973) has been cited by 43 publications

Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
The selective inhibition of the Syk tyrosine kinase ameliorates experimental autoimmune arthritis [ Front Immunol, 2023, 14:1279155] PubMed: 38111569
Bacterial DNA promoting inflammation via the Sgk1/Nedd4L/Syk pathway in mast cells contributes to antihistamine non-responsive CSU [ J Leukoc Biol, 2023, qiad025] PubMed: 36857592
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 [ Life Sci Alliance, 2023, 6(11)e202302106] PubMed: 37699657
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 [ Life Sci Alliance, 2023, 6(11)e202302106] PubMed: 37699657
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304] PubMed: 35704690
Interleukin 33-mediated inhibition of A-type K+ channels induces sensory neuronal hyperexcitability and nociceptive behaviors in mice [ Theranostics, 2022, 12(5):2232-2247] PubMed: 35265208
Targeting cellular iron homeostasis with ironomycin in diffuse large B cell lymphoma [ Cancer Res, 2022, canres.0218.2021] PubMed: 35078814
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746

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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.

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