| Identification | Back Directory | [Name]
Entospletinib (GS-9973) | [CAS]
1229208-44-9 | [Synonyms]
GS-9973
Entospletinib
GS-9973, Entospletinib
Entospletinib (GS-9973)
Entospletinib Dimesylate
6-(1H-indazol-6-yl)-N-(4-morpholinophenyl)imidazo[1,2-a]pyrazin-8-amine
6-(1H-Indazol-6-yl)-N-[4-(4-morpholinyl)phenyl]imidazo[1,2-a]pyrazin-8-amine | [Molecular Formula]
C23H21N7O | [MDL Number]
MFCD28099806 | [MOL File]
1229208-44-9.mol | [Molecular Weight]
411.459 |
| Chemical Properties | Back Directory | [density ]
1.45±0.1 g/cm3(Predicted) | [storage temp. ]
Desiccate at -20°C | [solubility ]
insoluble in EtOH; insoluble in H2O; ≥20.55 mg/mL in DMSO | [form ]
solid | [pka]
12.54±0.40(Predicted) |
| Questions And Answer | Back Directory | [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. | [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. The combination of idelalisib and GS-9973 synergistically inhibits CLL cell viability and further disrupts chemokine signaling. | [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 . |
| Hazard Information | Back Directory | [Uses]
GS 9973 is a selective and orally bioavailable inhibitor of spleen tyrosine kinase (Syk). | [target]
Syk | [References]
[1]. currie ks, kropf je, lee t, et al. discovery of gs-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase. j med chem, 2014, 57(9): 3856-3873.
[2]. burke rt1, meadows s, loriaux mm, 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, 5(4): 908-915.
[3]. sharman j, hawkins m, kolibaba k, et al. an open-label phase 2 trial of entospletinib (gs-9973), a selective spleen tyrosine kinase inhibitor, in chronic lymphocytic leukemia. blood, 2015, 125(15): 2336-2343. |
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