Home Angiogenesis Syk inhibitor Entospletinib (GS-9973) For research use only.

Entospletinib (GS-9973)

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.

Entospletinib (GS-9973) Chemical Structure

Entospletinib (GS-9973) Chemical Structure

CAS No. 1229208-44-9

Purity & Quality Control

Entospletinib (GS-9973) Related Products

Signaling Pathway

Syk Signaling Pathways

Syk Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MV411 cells  Proliferation assay 72 h Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry, EC50=0.327 μM 24779514
C57BL/6 mouse bone marrow cells Cytotoxic assay 4 days Cytotoxicity against C57BL/6 mouse bone marrow cells assessed as growth inhibition preincubated for 4 days followed by [3H]-thymidine addition measured after 5 hrs by betaplate counting analysis, IC50=0.582 μM 25633741
Ramos cells Function assay Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay, EC50=0.026μM 24779514
B-cells Function assay 1 hr Inhibition of Syk in alphaIgM-stimulated human B cells assessed as cell proliferation after 1 hr incubation by flow cytometry, EC50=0.041μM 24779514
B-cells Function assay 1 hr Inhibition of Syk in alphaIgM-stimulated human B cells assessed as CD86 expression after 1 hr incubation by flow cytometry, EC50=0.125μM 24779514
mast cells Function assay 1 hr Inhibition of cKit in stem cell factor-stimulated bone marrow derived mouse mast cells assessed as phosphorylation after 1 hr incubation, EC50=0.445μM 24779514
TF1 Function assay 1 hr Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation, EC50=0.453μM 24779514
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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.
Features Orally bioavailable Syk-selective inhibitor that has been tested in Phase II clinical trials for treatment of Haematological Malignancies.
Targets
Syk [1]
(Cell-free assay)
7.7 nM
In vitro
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]
Kinase Assay 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 Research 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-ERBB2 / ERBB2 / pEGFR / EGFR SYK / p-SYK 31492560
In Vivo
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]
Animal Research Animal Models Rat Collagen-Induced Arthritis (CIA) Model
Dosages ~10 mg/kg bid
Administration p.o.

Chemical Information & Solubility

Molecular Weight 411.46 Formula

C23H21N7O
CAS No. 1229208-44-9 SDF Download Entospletinib (GS-9973) SDF
Smiles C1COCCN1C2=CC=C(C=C2)NC3=NC(=CN4C3=NC=C4)C5=CC6=C(C=C5)C=NN6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 27 mg/mL ( (65.61 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Frequently Asked Questions

Question 1:
How should we use S7523 to perform intraperitoneal injection in mice?

Answer:
S7523 can be dissolved in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O at up to 2.5mg/ml and use it for intra peritoneal injection in mice. When making this vehicle, please dissolve the product in DMSO first, then add PEG 300 and Tween 80 and dilute with water as a final step.

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