Entospletinib (GS-9973) (C09-0880-873)

InformationEntospletinib (GS-9973) 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.TargetsSyk (Cell-free assay) 7.7 nMIn vitroGS-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 vivoGS-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 .Cell Research(from reference)Cell lines：MV-4-11 cells Concentrations：~10 μM Incubation Time：72 hours. Specification: 0.98 Molecular Formula: C23H21N7O Molecular Weight: 411.46 PubChem CID: 59473233 Isomeric SMILES: C1COCCN1C2=CC=C(C=C2)NC3=NC(=CN4C3=NC=C4)C5=CC6=C(C=C5)C=NN6 Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/E413770-SCI_046d0fe7033b21036a866c7ba462d3ed.pdf