产品说明书

Entospletinib

Print
Chemical Structure| 1229208-44-9 同义名 : GS-9973
CAS号 : 1229208-44-9
货号 : A181632
分子式 : C23H21N7O
纯度 : 99%+
分子量 : 411.459
MDL号 : MFCD28099806
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(109.37 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 0.4 mg/mL clear

PO 0.5% CMC-Na 41 mg/mL suspension

生物活性
靶点

  • Syk

    Syk, IC50:7.7 nM
描述 Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that mediates immunoreceptor signaling primarily in hematopoietic cells. GS-9973 is a potent, selective, and orally bioavailable Sky inhibitor with an EC50 value of 26 nM[1]. The level of phosphorylated Akt and ribosomal S6 in primary chronic lymphocytic leukemia (CLL) cells was decreased by 100 nM GS-9973 compared to control cells, while idelalisib and GS-9973 in combination (100 nM each) showed more potent inhibitory effect on Akt and ribosomal S6 phosphorylation. Compared to single agent treatment, the combination of GS-9973 (0.01 - 10 μM) and idelalisib (0.01 - 10 μM) synergistically decreased the cell viability of CLL cells isolated from the peripheral blood or bone marrow[2]. In a rat collagen-induced arthritis model, twice daily oral dosing with GS-9973 at 10, 3, and 1 mg/kg significantly inhibited ankle inflammation. Histological analyses showed that GS-9973 inhibited cartilage damage, bone resorption, pannus formation, and peritosteal bone formation with ED50 values ranging from 1.2 to 3.9 mg/kg[1].
作用机制 GS-9973 is a selective, orally efficacious, imidazopyrazine-based inhibitor of Syk that forms a hydrogen bond with the D512 side chain of Syk kinase[1].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
C57BL/6 mouse bone marrow cells Cytotoxic assay 4 days Cytotoxicity against C57BL/6 mouse bone marrow cells assessed as growth inhibition preincubated for 4 days followed by [3H]-thymidine addition measured after 5 hrs by betaplate counting analysis, IC50=0.582 μM 25633741
human MV411 cells Proliferation assay 72 h Inhibition of Flt3 in human MV411 cells assessed as assessed as proliferation after 72 hrs incubation by spectrophotometry, EC50=0.327 μM 24779514
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.43mL

0.49mL

0.24mL

12.15mL

2.43mL

1.22mL

24.30mL

4.86mL

2.43mL
参考文献

[1]Currie KS, Kropf JE, et al. Discovery of GS-9973, a selective and orally efficacious inhibitor of spleen tyrosine kinase. J Med Chem. 2014;57(9):3856-73.

[2]Burke RT, Meadows S, 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):908-15.

[3]Sun H, Lin DC, et al. Identification of a Novel SYK/c-MYC/MALAT1 Signaling Pathway and Its Potential Therapeutic Value in Ewing Sarcoma. Clin Cancer Res. 2017 Aug 1;23(15):4376-4387.