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CGI-1746

Catalog No.
A3302
Btk抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,200.00
现货
10mg
¥ 1,550.00
现货
50mg
¥ 5,400.00
现货
100mg
¥ 9,400.00
Ship with 10-15 days

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Background

CGI-1746 is a selective and potent inhibitor of Bruton's tyrosine kinase (BTK) with IC50 value of 1.9 nM [1][2].
Bruton’s tyrosine kinase (BTK) is a member of the Tec tyrosine kinase family and plays an important role in differentiation, proliferation and development of B cells. It is an attractive target for the treatment of immunological disorders such as B-cell malignancies, rheumatoid arthritis (RA), multiple sclerosis (MS) and lupus [3].
CGI-1746 potently inhibits both auto- and transphosphorylation of BTK. It binds to un-phosphorylated BTK and stabilizes it in an inactive enzyme state. In cellular assays, CGI-1746 blocks BCR-mediated B-cell proliferation and suppresses the production of IL-6, IL-1βand TNF in macrophages [1].
In experimental mouse models, CGI-1746 shows a robust anti-arthritic activity [1]. In B10.RIII mice model, CGI1746 resulted in a significant inhibition (97%) of clinical arthritis scores, which were better than dexamethasone treatment (56% inhibition) [2].
References:
[1]. Akinleye A, Chen Y, Mukhi N, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol, 2013, 6: 59.
[2]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50.
[3]. Young WB, Barbosa J, Blomgren P, et al. Potent and selective Bruton's tyrosine kinase inhibitors: discovery of GDC-0834. Bioorg Med Chem Lett, 2015, 25(6): 1333-1337.

文献引用

1. Mueller-Ortiz SL, Calame DG, et al. "The Complement Anaphylatoxins C5a and C3a Suppress IFN-β Production in Response to Listeria monocytogenes by Inhibition of the Cyclic Dinucleotide-Activated Cytosolic Surveillance Pathway." J Immunol. 2017 Apr 15;198(8):3237-3244. PMID:28275134

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt579.71
Cas No.910232-84-7
FormulaC34H37N5O4
SynonymsCGI1746;CGI 1746
Solubility≥29 mg/mL in DMSO, ≥6.72 mg/mL in EtOH with ultrasonic and warming, insoluble in H2O
Chemical Name4-tert-butyl-N-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide
SDFDownload SDF
Canonical SMILESCC1=C(C=CC=C1NC(=O)C2=CC=C(C=C2)C(C)(C)C)C3=CN(C(=O)C(=N3)NC4=CC=C(C=C4)C(=O)N5CCOCC5)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

人B细胞

制备方法

在DMSO中的溶解度大于29 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

0.003 ~ 10 μM

实验结果

在人B细胞中,CGI-1746有效抑制抗IgM诱导的Btk Tyr223、Btk Tyr551和PLCγ2 Tyr1217磷酸化,其平均IC50值为2.9 nM。此外,CGI-1746降低Btk Tyr551和Tyr223基础磷酸化水平,但不降低PLCγ2 Tyr1217基础磷酸化水平。

动物实验 [1]:

动物模型

胶原诱导的小鼠关节炎 (CIA) 模型

给药剂量

100 mg/kg;皮下注射;每天2次,从第12天到第26天

实验结果

CGI-1746显著抑制临床关节炎得分(97%的抑制)。此外,CGI-1746显著降低抗胶原II (CII) 滴度。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50.

生物活性

Description CGI1746是一种强效的和高选择性的Btk小分子抑制剂,IC50值为1.9 nM。
靶点 Btk          
IC50 1.9 nM          

质量控制

质量控制和MSDS

批次:

化学结构

CGI-1746

相关生物数据

CGI-1746