Entospletinib (GS-9973)

Catalog No.S7523

For research use only.

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

CAS No. 1229208-44-9

Selleck's Entospletinib (GS-9973) has been cited by 33 publications

Purity & Quality Control

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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

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 idelalisib and GS-9973 synergistically inhibits CLL cell viability and further disrupts chemokine signaling. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MV411 cells  MmHyVJJwdGmoZYLheIlwdiCjc4PhfS=> MYq3NkBp M334[2lvcGmkaYTpc44hd2ZiRnz0N{BqdiCqdX3hckBOXjRzMTDj[YxteyCjc4Pld5Nm\CCjczDhd5Nme3OnZDDhd{Bxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BqdmO3YnH0bY9vKGK7IIPw[YN1em:yaH;0c41mfHK7LDDFR|UxRTBwM{K3JO69VQ>? Ml3zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5N{m1NVQoRjJ2N{e5OVE1RC:jPh?=
C57BL/6 mouse bone marrow cells MUTDfZRwfG:6aXRCpIF{e2G7 NGPj[JE1KGSjeYO= MUPDfZRwfG:6aXPpeJkh[WejaX7zeEBEPTeETD:2JI1wfXOnIHLvcoUhdWG{cn;3JINmdGy|IHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJJBz\WmwY4XiZZRm\CCob4KgOEBl[Xm|IH\vcIxwf2WmIHL5JHs{UF1vdHj5cYllcW6nIHHk[Il1cW:wIH3lZZN2emWmIHHmeIVzKDViaILzJIJ6KGKndHHwcIF1\SClb4XueIlv\yCjbnHsfZNqeyxiSVO1NF0xNjV6MjFOwG0> NX;NW5pZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2N|M4PDFpPkK1OlM{PzRzPD;hQi=>
Ramos cells MkPjSpVv[3Srb36gZZN{[Xl? M4r5fWlvcGmkaYTpc44hd2ZiU4nrJIlvKGGwdHnoeY1idiCLZ12td5RqdXWuYYTl[EBpfW2jbjDSZY1weyClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDCR3IudWWmaXH0[YQhSkyQSzDwbI9{eGixconsZZRqd25iYomgZ4VtdHWuYYKgZZN{[XluIFXDOVA:OC5yMkdOwG0> NFvBe489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O|k2OTR:L3G+
B-cells NV25boxqTnWwY4Tpc44h[XO|YYm= M3XIVVEhcHJ? Ml3OTY5pcWKrdHnvckBw\iCVeXugbY4h[WyyaHHJ[20ue3SrbYXsZZRm\CCqdX3hckBDKGOnbHzzJIF{e2W|c3XkJIF{KGOnbHygdJJwdGmoZYLheIlwdiCjZoTldkAyKGi{IHnuZ5Vj[XSrb36gZpkh\myxdzDjfZRwdWW2comsJGVEPTB;MD6wOFHPxE1? MlK2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5N{m1NVQoRjJ2N{e5OVE1RC:jPh?=
B-cells M{nzcGZ2dmO2aX;uJIF{e2G7 NInBT2oyKGi{ NIjGSIFKdmirYnn0bY9vKG:oIGP5b{BqdiCjbIDoZWloVS2|dHnteYxifGWmIHj1cYFvKEJiY3XscJMh[XO|ZYPz[YQh[XNiQ1S4OkBmgHC{ZYPzbY9vKGGodHXyJFEhcHJiaX7jeYJifGmxbjDifUBndG:5IHP5eI9u\XS{eTygSWM2OD1yLkGyOe69VQ>? MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
mast cells MYnGeY5kfGmxbjDhd5NigQ>? Mn\1NUBpeg>? NIHX[I5KdmirYnn0bY9vKG:oIHPLbZQhcW5ic4TlcUBk\WyuIH\hZ5Rwei2|dHnteYxifGWmIHLvcoUhdWG{cn;3JIRmemm4ZXSgcY92e2VibXHzeEBk\WyuczDhd5Nme3OnZDDhd{BxcG:|cHjvdplt[XSrb36gZYZ1\XJiMTDodkBqdmO3YnH0bY9vNCCHQ{WwQVAvPDR3zszN NGqybVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O|k2OTR:L3G+
TF1 M1LUOmZ2dmO2aX;uJIF{e2G7 NEKyeFcyKGi{ NE[weGxKdmirYnn0bY9vKG:oIFrhb|IhcW5iZYL5eIhzd3CxaXX0bY4ue3SrbYXsZZRm\CCqdX3hckBVTjFiY3XscJMh[XO|ZYPz[YQh[XNiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3TeIF1PSCjZoTldkAyKGi{IHnuZ5Vj[XSrb36sJGVEPTB;MD60OVPPxE1? MmDKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5N{m1NVQoRjJ2N{e5OVE1RC:jPh?=
Assay
Methods Test Index PMID
Western blot p-ERBB2 / ERBB2 / pEGFR / EGFR ; SYK / p-SYK 31492560 29537660
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]

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, 0.25% glycerol, 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:

[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 Research:

[1]

  • Animal Models: Rat Collagen-Induced Arthritis (CIA) Model
  • Dosages: ~10 mg/kg bid
  • Administration: p.o.

Solubility (25°C)

In vitro

DMSO 26 mg/mL warmed
(63.18 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.

2.5mg/mL

Chemical Information

Molecular Weight 411.46
Formula

C23H21N7O

CAS No. 1229208-44-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1COCCN1C2=CC=C(C=C2)NC3=NC(=CN4C3=NC=C4)C5=CC6=C(C=C5)C=NN6

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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.

Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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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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