Biological Activity
Entospletinib (GS-9973) is an orally bioavailable, selective?Syk inhibitor with an IC50 of 7.7 nM.
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].
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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.