Lanraplenib succinate (GS-9876 succinate) 是一种高度选择性的口服 SYK 抑制剂 (IC50=9.5 nM) ，用于治疗炎症性疾病。Lanraplenib succinate (GS-9876 succinate) 通过糖蛋白 VI (GPVI) 受体抑制血小板中的 SYK 活性，而不会延长猴子或人类的出血时间 (BT)。
货号:ajcx15088
CAS:1800047-00-0
分子式:C23H25N9O.3/2C4H6O4
分子量：620.64
溶解度:DMSO: 83.33 mg/mL (134.26 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

Lanraplenib succinate (GS-9876 succinate) is a highly selective and orally active SYK inhibitor (IC50=9.5 nM) in development for the treatment of inflammatory diseases. Lanraplenib succinate (GS-9876 succinate) inhibits SYK activity in platelets via the glycoprotein VI (GPVI) receptor without prolonging bleeding time (BT) in monkeys or humans[1][2][3].

Lanraplenib succinate (GS-9876 succinate) inhibits anti-IgM stimulated phosphorylation of AKT, BLNK, BTK, ERK, MEK, and PKCδ in human B cells with EC50 values of 24-51 nM. Lanraplenib monosuccinate 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, Lanraplenib succinate inhibits IC-stimulated TNFα and IL-1β release (EC50=121±77 nM and 9±17 nM, respectively)[1].Lanraplenib succinate (GS-9876 succinate) 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[2].

[1]. Di Paolo J, et al. FRI0049 Preclinical Characterization of GS-9876, A Novel, Oral SYK Inhibitor That Shows Efficacy in Multiple Established Rat Models of Collagen-Induced Arthritis.Annals of the Rheumatic Diseases 2016;75:443-444. [2]. Clarke AS, et al. Effects of GS-9876, a novel spleen tyrosine kinase inhibitor, on platelet function and systemic hemostasis. Thromb Res. 2018 Oct;170:109-118. [3]. Kivitz AJ, et al. GS-9876, a Novel, Highly Selective, SYK Inhibitor in Patients with Active Rheumatoid Arthritis: Safety, Tolerability and Efficacy Results of a Phase 2 Study [abstract]. Arthritis Rheumatol.2018; 70 (suppl 10).