切换导航

ST 2825

Catalog No.
A3840
MyD88二聚化抑制剂
组合的产品项目
规格价格库存 数量
1mg
¥ 3,962.00
现货
5mg
¥ 13,615.00
Ship with 10-15 days
10mg
¥ 20,713.00
Ship with 10-15 days

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

ST 2825 is a specific inhibitor of MyD88 dimerization [1].

ST 2825 is a synthetic compound which mimics the structure of the heptapeptide in the BB-loop of the MyD88-TIR domain and interferes the homodimerization of MyD88. ST 2825 was proved to specifically inhibit the homodimerization of MyD88 TIR domains without affecting the homodimerization of death domains. In HEK293T cells transfected with Flag-MyD88 and Myc-MyD88, ST 2825 inhibited the interaction of the two MyD88 by 80% at the concentration of 10 μM. This inhibition resulted in the subsequent interference of the IRAK1 and IRAK4 recruitment. Besides that, administration of ST 2825 significantly inhibited the IL-6 production stimulated by IL-1β at doses of 100 and 200 mg/kg in mice. Furthermore, 8 μM ST 2825 completely blocked the TLR9-induced B cell proliferation. ST2825 also suppressed the generation of plasma cells induced by CpG dose-dependently [1].

References:
[1] Loiarro M, Capolunghi F, Fantò N, et al. Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. Journal of leukocyte biology, 2007, 82(4): 801-810.

文献引用

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt591.51
Cas No.894787-30-5
FormulaC27H28Cl2N4O5S
SynonymsST2825;ST-2825
SolubilitySoluble in DMSO
Chemical Name(4R,7R,8aR)-1'-[2-[4-[[2-(2,4-dichlorophenoxy)acetyl]amino]phenyl]acetyl]-6-oxospiro[3,4,8,8a-tetrahydro-2H-pyrrolo[2,1-b][1,3]thiazine-7,2'-pyrrolidine]-4-carboxamide
SDFDownload SDF
Canonical SMILESC1CC2(CC3N(C2=O)C(CCS3)C(=O)N)N(C1)C(=O)CC4=CC=C(C=C4)NC(=O)COC5=C(C=C(C=C5)Cl)Cl
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

HEK 293T和HeLa细胞[1],B细胞和浆细胞样树突细胞[1]。

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

6-7 h(HEK 293T细胞)、15 min(HeLa细胞)、5天(B细胞培养)[1]

应用

在HEK293T细胞中,ST2825特异性地抑制MyD88 TIR结构域的同源二聚化,在5 μM和10 μM时分别获得40%和80%的抑制。该效应对TIR结构域的同源二聚化是特异性的,而对死亡结构域的同源二聚化不起作用。而且,ST2825干扰MyD88对IRAK1和IRAK4的募集,从而抑制IL-1介导的NF-κB转录活性的激活[1]。CpG诱导TLR9的激活,从而诱导B细胞增殖和分化形成浆细胞,而ST2825(> 8 μM)可以抑制该反应。这些结果表明,ST2825通过干扰MyD88的同源二聚化,从而阻断IL-1R/TLR信号。ST2825可能具有治疗慢性炎性疾病的潜力[1]。在来自SLE患者的外周血单核细胞中,ST2825阻断TLR9诱导的浆细胞(PC)的生成[3]。

动物实验[2]:

动物模型

雌性C57BL小鼠[1]

剂量

100或200 mg/kg/day;口服给药[1];25 mg/kg/day,注射[2]

准备方法

ST2825溶于0.5%羧甲基纤维素[1]

应用

在治疗小鼠中,ST2825(100或200 mg/kg/day)剂量依赖地抑制IL-1β诱导的IL-6的产生[1]。在非再灌注急性心肌梗塞小鼠模型中,ST2825(25 mg/kg)防止左心室扩张和肥厚,而梗死面积没有显著减少[2]。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1]. Loiarro M, Capolunghi F, Fantò N et al. Pivotal advance: inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. Journal of Leukocyte Biology (2007), 82(4), 801-810.

[2]. Van Tassell BW, Seropian IM, Toldo S et al. Pharmacologic Inhibition of Myeloid Differentiation Factor 88 (MyD88) Prevents Left Ventricular Dilation and Hypertrophy After Experimental Acute Myocardial Infarction in the Mouse. Journal of Cardiovascular Pharmacology (2010), 55(4), 385-390.

[3]. Capolunghi F1, Rosado MM, Cascioli S et al., Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology (Oxford). 2010 Dec;49(12):2281-9.

生物活性

描述 ST2825是MyD88抑制剂。
靶点 MyD88          
IC50            

质量控制

质量控制和MSDS

批次:

化学结构

ST 2825

相关生物数据

ST 2825

相关生物数据

ST 2825

相关生物数据

ST 2825

相关生物数据

ST 2825