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Purity: ≥98%
Description: Entospletinib (formerly known as GS-9973) is a novel, potent, orally bioavailable, and highly selective Syk inhibitor with potential anti-inflammatory and immunomodulatory activities. It inhibits Syk with an IC50 of 7.7 nM in a cell-free assay. Entospletinib displayed high in vivo anti-inflammatory activity in Rat Collagen-Induced Arthritis (CIA) Model. In monocytes, GS-9973 inhibited immune-complex-stimulated cytokine production and BCR-mediated proliferation and activation of B-cells. In chronic lymphocytic leukemia (CLL) cells, GS-9973 significantly reduced pAkt and ribosomal S6 phosphorylation. These results suggested that GS-9973 inhibited B-cell receptor (BCR) mediated signaling pathways.
| ln Vitro |
Good bidirectional permeability to Caco-2 cell monolayers is demonstrated in vitro by entospletinib (GS-9973). Entospletinib (GS-9973) is a cell-based medication that shows good selectivity for Syk and efficiently suppresses immunological complex-stimulated cytokine production in monocytes as well as BCR-mediated B cell activation and proliferation [1]. Entospletinib (GS-9973) and Idelalisib work together to suppress CLL cell viability and further impede chemokine signaling [2].
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| ln Vivo |
In rats and dogs, entespletinib (GS-9973) (1 mg/kg, po) has a moderate to high bioavailability. In a rat model of collagen-induced arthritis, entospletinib (GS-9973) (1–10 mg/kg, po) markedly reduced ankle inflammation. Furthermore, Entospletinib (GS-9973) showed disease-modifying activity in several histological measurements, with an ED50 ranging from 1.2 to 3.9 mg/kg[1]. These measurements included inhibition of pannus formation, cartilage damage, bone resorption, and periosteal bone formation.
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| 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.
[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 |
| Molecular Formula |
C23H21N7O
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| Molecular Weight |
411.46
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| CAS # |
1229208-44-9
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| Related CAS # |
1648797-46-9 (dimesylate);1229208-44-9;
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| SMILES |
C12=NC=CN1C=C(C3=CC4=C(C=C3)C=NN4)N=C2NC5=CC=C(N6CCOCC6)C=C5
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| InChi Key |
XSMSNFMDVXXHGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H21N7O/c1-2-17-14-25-28-20(17)13-16(1)21-15-30-8-7-24-23(30)22(27-21)26-18-3-5-19(6-4-18)29-9-11-31-12-10-29/h1-8,13-15H,9-12H2,(H,25,28)(H,26,27)
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| Chemical Name |
6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine
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| Synonyms |
GS-9973; Entospletinib; GS9973; GS 9973;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03010358 | Completed Has Results | Drug: Entospletinib Other: Laboratory Biomarker Analysis |
Anemia B-Cell Prolymphocytic Leukemia |
Alexey Danilov, MD | July 17, 2017 | Phase 1 Phase 2 |
| NCT02521376 | Completed Has Results | Drug: Entospletinib | Oncology | Gilead Sciences | November 16, 2015 | Phase 1 |
| NCT01796470 | Terminated Has Results | Drug: Entospletinib Drug: Idelalisib |
Chronic Lymphocytic Leukemia Mantle Cell Lymphoma |
Gilead Sciences | June 20, 2013 | Phase 2 |
| NCT05020665 | Terminated Has Results | Drug: Entospletinib Drug: Placebo |
Nucleophosmin 1-mutated Acute Myeloid Leukemia |
Kronos Bio | November 24, 2021 | Phase 3 |
Treatment of primary CLL cells (n =14) co-cultured with HS5 stromal cells with idelalisib (100 nM) or GS-9973 (100 nM), alone or in combination (100 nM each), results in decreased AKT phosphorylation.Oncotarget.2014 Feb 28;5(4):908-15. |
Disease status and biologic CLL disease characteristics.Oncotarget.2014 Feb 28;5(4):908-15. |
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