Lanraplenib (GS-9876, GS-SYK) 是一种有效的、高选择性的 Spleen Tyrosine Kinase (SYK) 的口服活性抑制剂，其IC50值为9.5 nM。Lanraplenib 通过 glycoprotein VI (GPVI) receptor 抑制血小板中的SYK活性，而不会延长猴子或人类的出血时间(BT)。 Information Lanraplenib (GS-9876) Lanraplenib (GS-9876, GS-SYK) is a potent, highly selective and orally active inhibitor of Spleen Tyrosine Kinase (SYK) with IC50 of 9.5 nM. Lanraplenib inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans. Targets GPVI receptor ; Syk (Cell-free assay) ; 9.5 nM In vitro GS-9876 inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24–51 nM. Functionally, GS-9876 inhibits anti-IgM mediated CD69 and CD86 expression on B-cells (EC50=112±10 nM and 164±15 nM, respectively) and anti-IgM /anti-CD40 co-stimulated B cell proliferation (EC50=108±55 nM). In human macrophages, GS-9876 inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively). Anti-CD3/anti-CD28 stimulated T cell proliferation is weakly inhibited (EC50=1291±398 nM), with selectivity >10-fold versus the inhibition of B cell proliferation. In human blood, GS-9876 blocks SYK phosphorylation, CD69 expression on B cells, and CD63 expression in basophils.\xa0GS-9876 inhibits glycoprotein VI (GPVI)-induced phosphorylation of linker for activation of T cells and phospholipase Cγ2, platelet activation and aggregation in human whole blood, and platelet binding to collagen under arterial flow. In vivo GS-9876 demonstrates a dose-dependent improvement in clinical score and histopathology parameters with once-daily dosing in short and long term rat models of collagen-induced arthritis (CIA). Significant efficacy can be achieved with GS-9876 doses that produces trough pSYK inhibition of Cell Research(from reference) Cell lines：Human blood platelets Concentrations：0.01 μM to 100 μM Incubation Time：15 min
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Lanraplenib (GS-9876)
CAS number：1800046-95-0 molecular formula：C23H25N9O
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| Chinese alias | 兰拉普利尼 (GS-9876) | ||
| English alias | DB14770 | Lanraplenib (GS-9876) | AC-36571 | InChI=1/C3H6ClNO2/c4-1-2(5)3(6)7/h2H,1,5H2,(H,6,7)/t2-/m0/s1 | EX-A3747 | XCIGZBVOUQVIPI-UHFFFAOYSA-N | 6-(6-amino-2-pyrazinyl)-N-[4-[4-(3-oxetanyl)-1-piperazinyl]phenyl]-imidazo[1,2-a] | ||
| CAS number | 1800046-95-0 | molecular formula | C23H25N9O |
| molecular weight | 443.5 g/mol | Exact mass | - |
| PSA | 110.000 Ų | logp | 1.211 |
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