Cat. No.: HY-15968

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Entospletinib

(Synonyms: GS-9973)

12 Cited Publications

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Based on 12 publication(s) in Google Scholar

Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with an IC₅₀ of 7.7 nM.

For research use only. We do not sell to patients.

Purity: 99.49%
CAS No.: 1229208-44-9
Formula: C₂₃H₂₁N₇O
Molecular Weight:411.46

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Entospletinib Chemical Structure

CAS No.: 1229208-44-9

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (12)
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with an IC₅₀ of 7.7 nM.

IC₅₀ & Target

IC50: 7.7 nM (Syk)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human A549 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human A549 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
BaF3	IC₅₀	32 nM Compound: GS-9973	Antiproliferative activity against mouse BaF3 cells harboring TEL/SYK incubated for 72 hrs by CellTiter-Glo assay Antiproliferative activity against mouse BaF3 cells harboring TEL/SYK incubated for 72 hrs by CellTiter-Glo assay	[PMID: 38604095]
BaF3	IC₅₀	5577 nM Compound: GS-9973	Antiproliferative activity against IL3 stimulated mouse BaF3 cells harboring TEL/SYK incubated for 72 hrs by CellTiter-Glo assay Antiproliferative activity against IL3 stimulated mouse BaF3 cells harboring TEL/SYK incubated for 72 hrs by CellTiter-Glo assay	[PMID: 38604095]
Bone marrow cell	IC₅₀	582 nM Compound: 2, GS-9973	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 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	[PMID: 25633741]
Caco-2	IC₅₀	6.86 μM Compound: 173	Cytotoxicity against human Caco-2 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human Caco-2 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
ES-2	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human ES2 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human ES2 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
HEY	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human HEY cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human HEY cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
HUVEC	EC₅₀	>1000 nM Compound: 68, GS-9973	Inhibition of KDR in VEGF-stimulated HUVEC assessed as phosphorylation after 1 hr incubation Inhibition of KDR in VEGF-stimulated HUVEC assessed as phosphorylation after 1 hr incubation	[PMID: 24779514]
MV4-11	EC₅₀	327 nM Compound: 68, GS-9973	Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry	[PMID: 24779514]
NCI-H1299	IC₅₀	6.26 μM Compound: 173	Cytotoxicity against human NCI-H1299 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human NCI-H1299 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
NCI-H460	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human NCI-H460 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human NCI-H460 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
OVCAR-5	IC₅₀	8.3 μM Compound: 173	Cytotoxicity against human OVCAR-5 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human OVCAR-5 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
Ramos	EC₅₀	26 nM Compound: 68, GS-9973	Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay Inhibition of Syk in antihuman IgM-stimulated human Ramos cells assessed as decrease in BCR-mediated BLNK phosphorylation by cellular assay	[PMID: 24779514]
Ramos	EC₅₀	2 nM Compound: 3; GS-9973	Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay	[PMID: 32292557]
SK-OV-3	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human SK-OV-3 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human SK-OV-3 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
SW626	IC₅₀	>10 μM Compound: 173	Cytotoxicity against human SW626 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay Cytotoxicity against human SW626 cells assessed as reduction in cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 37300915]
TF-1	EC₅₀	453 nM Compound: 68, GS-9973	Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation Inhibition of Jak2 in erythropoietin-stimulated human TF1 cells assessed as assessed as phospho-Stat5 after 1 hr incubation	[PMID: 24779514]

In Vitro

Entospletinib (GS-9973) shows good bidirectional permeability across Caco-2 cell monolayers in vitro. In cells, Entospletinib (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 Entospletinib (GS-9973) synergistically inhibits CLL cell viability and further disrupts chemokine signaling^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Entospletinib (GS-9973) (1 mg/kg, p.o.) shows moderate to high bioavailability in rat and dog. In a rat collagen-induced arthritis model, Entospletinib (GS-9973) (1-10 mg/kg, p.o.) significantly inhibits ankle inflammation. Moreover, Entospletinib (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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 1229208-44-9
Appearance Solid
Molecular Weight 411.46
Formula C₂₃H₂₁N₇O
Color White to off-white
SMILES

C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5
Synonyms

GS-9973
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (12)

All In Vivo Efficacy StudyIn Vivo ImagingIHC

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Journal Impact Factor

Nat Commun

Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State. [Abstract]

2026 Feb 12;17(1):1214. PMID: 41680175
Cell Rep

Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages. [Abstract]

2024 Sep 13;43(9):114741. PMID: 39276347
Cell Rep

Podocyte SIRPα reduction aggravates lupus nephritis via promoting T cell inflammatory responses. [Abstract]

2024 May 16;43(5):114249. PMID: 38758648
Mol Cancer Ther

AKT Inhibition Sensitizes to Polo-Like Kinase 1 Inhibitor Onvansertib in Prostate Cancer. [Abstract]

2024 Oct 1;23(10):1404-1417. PMID: 38894678
Eur J Med Chem

Scaffold hopping of the SYK inhibitor entospletinib leads to broader targeting of the BCR signalosome. [Abstract]

2020 Oct 15;204:112636. PMID: 32731189
J Bone Miner Res

Alveolar Bone Protection by Targeting the SH3BP2-SYK Axis in Osteoclasts. [Abstract]

2020 Feb;35(2):382-395. PMID: 31613396
J Bone Miner Res

Second-Generation SYK Inhibitor Entospletinib Ameliorates Fully Established Inflammation and Bone Destruction in the Cherubism Mouse Model. [Abstract]

2018 Aug;33(8):1513-1519. PMID: 29669173

Entospletinib purchased from MedChemExpress. Usage Cited in: J Bone Miner Res. 2018 Aug;33(8):1513-1519. [Abstract]

Experimental sequence of Entospletinib (GS-9973, 100 mg/kg, daily) administration. 10-week-old Sh3bp2^+/+ and Sh3bp2^KI/KI mice were treated with 100 mg/kg of GS-9973 or DMSO every day for 6 weeks. Mice were euthanized at 16 weeks of age for analysis.

Entospletinib purchased from MedChemExpress. Usage Cited in: J Bone Miner Res. 2018 Aug;33(8):1513-1519. [Abstract]

Facial appearance of Entospletinib (GS-9973, 100 mg/kg, daily)- treated or DMSO-treated mice (top: before treatment at 10 weeks of age; bottom: after treatment at 16 weeks of age). Blue arrows indicate closed eyelids due to facial skin inflammation. GS-9973 treatment improved eyelid closure in Sh3bp2^KI/KI mice at 16 weeks old (red arrows). Numbers represent the percentage of Sh3bp2^KI/KI mice with improved facial swelling.

Entospletinib purchased from MedChemExpress. Usage Cited in: J Bone Miner Res. 2018 Aug;33(8):1513-1519. [Abstract]

Liver sections from Entospletinib (GS-9973, 100 mg/kg, daily)-treated or DMSO-treated Sh3bp2^+/+ and Sh3bp2^KI/KI mice (H&E). Arrows indicate inflammatory infiltrates.

Entospletinib purchased from MedChemExpress. Usage Cited in: J Bone Miner Res. 2018 Aug;33(8):1513-1519. [Abstract]

Serum TNF-α levels of GS-9973-treated or DMSO-treated Sh3bp2^+/+ and Sh3bp2^KI/KI mice at 16 weeks old.

Entospletinib purchased from MedChemExpress. Usage Cited in: J Bone Miner Res. 2018 Aug;33(8):1513-1519. [Abstract]

3D μCT images of the ankle joint (top) and calcaneus (bottom) from 16-week-old Sh3bp2^+/+ and Sh3bp2^KI/KI mice treated with Entospletinib (GS-9973) or DMSO.
J Mol Cell Biol

FcεRIγ Reinforces Double-Negative T cell-mediated Antibody-dependent Cellular Cytotoxicity Against Tumor Cells. [Abstract]

2026 Jan 2:mjaf059. PMID: 41481135
Hematol Oncol

Gene Expression Profiling in Acute Myeloid Leukemia Patient Subgroups With High and Low Sensitivity Toward SYK Inhibitors. [Abstract]

2025 Mar;43(2):e70058. PMID: 40088478
Metabolomics

2026 Apr 17;22(3):51.
PLoS One

A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery. [Abstract]

2024 Nov 1;19(11):e0308647. PMID: 39485774
SSRN

2023 Dec 1.

Solvent & Solubility

In Vitro:

DMSO : 35 mg/mL (85.06 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.4304 mL

12.1518 mL

24.3037 mL

5 mM

0.4861 mL

2.4304 mL

4.8607 mL

10 mM

0.2430 mL

1.2152 mL

2.4304 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

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Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (6.08 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protocol

Cell Assay^[1]

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°C. Alamar blue (10%) is added to the cells, which are incubated for an additional 12-18 h at 37°C, and inhibition of the relative cell numbers is determined by spectrophotometer readings at 570/600 nm.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[1]

Female Lewis rats (mean mass 178 g, eight per group for collagen arthritis, four per group for normal controls) are anesthetized with isoflurane and injected with 300 μL of Freund’s incomplete adjuvant containing 2 mg/mL bovine type II collagen at the base of the tail and two sites on the back on days 0 and 6. Oral dosing (bid at 12 h intervals) is performed on arthritic days 0-7 with vehicle (Cremophor/ethanol/saline), Entospletinib (GS-9973) (1, 3, or 10 mg/kg), or the reference compound dexamethasone (Dex; 0.075 mg/kg) administered daily (qd). Rats are terminated on arthritis day 16. Efficacy evaluation is based on animal body masses, daily ankle caliper measurements, ankle diameters expressed as the area under the curve (AUC), terminal hind paw masses, and histopathologic evaluation of ankles and knees. PK is measured from plasma samples taken 0, 2, 4, 8, 12, and 24 h post last dose. The paws are fixed in formalin and processed for hemotoxylin (H) and eosin (E) microscopy. H and E sections are scored for bone resorption as follows: (0) normal; (0.5) normal on low magnification but have the earliest hint of small areas of resorption in the metaphysis with no resorption in the tarsal bones; (1) (minimal) small definite areas of resorption in distal tibial trabecular or cortical bone or in the tarsal bones, not readily apparent on low magnification, rare osteoclasts; (2) (mild) more numerous areas (<25% loss of bone in growth plate area) of resorption in distal tibial trabecular or cortical bone and tarsals apparent on low magnification, osteoclasts more numerous; (3) (moderate) obvious resorption of medullary trabecular and cortical bone without full thickness defects in both distal tibial cortices, loss of some medullary trabeculae with 26-50% loss across the growth plate and cortices, some loss in tarsal bones, lesion apparent on low magnification, osteoclasts more numerous; (4) (marked) full or nearly full thickness defects in both distal tibial cortices, often with distortion of the profile of the remaining cortical surface, marked loss of medullary bone of distal tibia (50-100% loss across the growth plate area and cortices and up to 50% loss in small tarsals if minor in tibia), numerous osteoclasts, minor to mild resorption in smaller tarsal bones; (5) (severe) full thickness defects in both distal tibial cortices with >75% loss across the growth plate and both cortices and >50% loss in tarsals, often with distortion of the profile of the remaining cortical surface, marked loss of medullary bone of distal tibia, numerous osteoclasts. Osteoclast counts (5400× fields) are performed on the ankles in the areas of greatest bone resorption.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (281 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Currie KS, et al. Discovery of GS-9973, a Selective and Orally Efficacious Inhibitor of Spleen Tyrosine Kinase. J Med Chem. 2014 May 8;57(9):3856-73. [Content Brief]

[2]. Burke RT, et al. A potential therapeutic strategy for chronic lymphocytic leukemia by combining Idelalisib and GS-9973, a novel spleen tyrosine kinase (Syk) inhibitor. Oncotarget. 2014 Feb 28;5(4):908-15. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.4304 mL	12.1518 mL	24.3037 mL	60.7592 mL
	5 mM	0.4861 mL	2.4304 mL	4.8607 mL	12.1518 mL
	10 mM	0.2430 mL	1.2152 mL	2.4304 mL	6.0759 mL
	15 mM	0.1620 mL	0.8101 mL	1.6202 mL	4.0506 mL
	20 mM	0.1215 mL	0.6076 mL	1.2152 mL	3.0380 mL
	25 mM	0.0972 mL	0.4861 mL	0.9721 mL	2.4304 mL
	30 mM	0.0810 mL	0.4051 mL	0.8101 mL	2.0253 mL
	40 mM	0.0608 mL	0.3038 mL	0.6076 mL	1.5190 mL
	50 mM	0.0486 mL	0.2430 mL	0.4861 mL	1.2152 mL
	60 mM	0.0405 mL	0.2025 mL	0.4051 mL	1.0127 mL
	80 mM	0.0304 mL	0.1519 mL	0.3038 mL	0.7595 mL

Keywords

Entospletinib

12 Cited Publications

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Entospletinib

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Publications Citing Use of MedChemExpress (MCE) Entospletinib

Biological Activity

Chemical Information

Publications (12)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Entospletinib

Anti-Infection Compound Library

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

Protein Tyrosine Kinase Compound Library

Anti-Cancer Compound Library

Clinical Compound Library

Drug Repurposing Compound Library

Anti-COVID-19 Compound Library

Orally Active Compound Library

Chemical Probe Library

Rare Diseases Drug Library

Human Metabolite Library

Highly Selective Inhibitors Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Mass Spectrometry Human Metabolite Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Entospletinib

Biological Activity

Chemical Information

Publications (12)

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Entospletinib Related Classifications

HY-15968 Related Classifications