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NSC 687852 (b-AP15)

现货
Catalog No.
A4453
19S调节颗粒抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
10mg
¥ 750.00
现货
50mg
¥ 2,430.00
现货
200mg
¥ 5,230.00
现货

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Background

IC50: N/A

NSC 687852 is a 19S regulatory particle inhibitor.

The 19S particles bind polyubiquitin-linked polypeptides and present them to the 20S degradative units. USP14 and UCHL5 are cysteine enzymes that become activated after being associated with the proteasome.

In vitro: NSC 687852 blocked deubiquitylating activity of USP14 and UCHL5 selectively without inhibiting proteasome activity. NSC 687852 decreased viability in multiple myeloma (MM) cell lines and patient MM cells, inhibited MM cell proliferation even in the presence of bone marrow stroma cells, and overcomed bortezomib resistance. Anti-MM activity of NSC 687852 was associated with growth arrest through downregulating CDC2, CDC25C, and cyclin B1, as well as induction of caspase-dependent apoptosis and activation of unfolded protein response [1].

In vivo: In vivo studies using distinct human MM xenograft models showed that NSC 687852 was well tolerated, inhibited tumor growth, and prolonged mouse survival. Combination of NSC 687852 with suberoylanilide hydroxamic acid, lenalidomide, or dexamethasone was found to induce synergistic anti-MM activity [1].

Clinical trial: N/A

Reference:
[1] Ze Tian,Padraig D'Arcy,Xin Wang,Arghya Ray,Yu-Tzu Tai,Yiguo Hu,Ruben D Carrasco,Paul Richardson,Stig Linder,Dharminder Chauhan,Kenneth C Anderson.  A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30; 123(5): 706–716.

Chemical Properties

StorageStore at 4°C
M.Wt419.39
Cas No.1009817-63-3
FormulaC22H17N3O6
Synonymsb-AP15
Solubility≥20.95mg/mL in DMSO, <2.19 mg/mL in EtOH, <2.42 mg/mL in H2O
Chemical Name(3E,5E)-3,5-bis[(4-nitrophenyl)methylidene]-1-prop-2-enoylpiperidin-4-one
SDFDownload SDF
Canonical SMILESC=CC(=O)N1CC(=CC2=CC=C(C=C2)[N+](=O)[O-])C(=O)C(=CC3=CC=C(C=C3)[N+](=O)[O-])C1
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

从成年雄性C57BL / 6小鼠(Harlan)制备的细菌脂多糖(LPS)诱导的巨噬细胞LPS引发的THP-1细胞(为了在nigericin处理前诱导前IL-1β表达)

溶解方法

该化合物在DMSO里面的溶解度>21mg/mL。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

1μM

应用

NSC 687852预处理能够抑制LPS诱导的腹膜巨噬细胞中ATP诱导的IL-1β释放和来自LPS引发的THP-1细胞中nigericin诱导的释放,并降低THP-1细胞中nigericin处理诱导的细胞死亡水平。在巨噬细胞中,NSC 687852也能导致聚泛素化蛋白酶体底物的增加。在LPS引发的THP-1细胞中,NSC 687852显著减少nigericin处理后形成的ASC斑点的数量。 类似地,NSC 687852也抑制了鼠腹膜巨噬细胞中ATP诱导的斑点形成。

动物实验[2]:

动物模型

携带FaDu鳞状细胞癌异种移植物的联合免疫缺陷(SCID)小鼠;过表达BCL2的HCT-116结肠癌异种移植物的小鼠

剂量

每日皮下注射; 5 mg/kg体重

应用

在具有FaDu鳞状细胞癌异种移植物的严重联合免疫缺陷(SCID)小鼠中,每日给予NSC 687852存在明显的抗肿瘤活性。通过测量循环中异种移植物衍生的CK18来分析肿瘤死亡,总CK18的血浆浓度显著增加,caspase切割的CK18(CK18-Asp396)浓度也增加,表明NSC 687852具有体内抗肿瘤细胞的活性。当检测过表达BCL2的HCT-116结肠癌异种移植物的小鼠的无疾病生存期时,与对照相比,NSC 687852处理明显延迟肿瘤发生,其中6例用NSC 687852处理的小鼠中有2例完全无病至研究结束。

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]. Lopez-Castejon G,Luheshi NM,Compan V., et al. Deubiquitinases regulate the activity of caspase-1 and interleukin-1β secretion via assembly of the inflammasome. J Biol Chem.2013 Jan 25;288(4):2721-33. doi: 10.1074/jbc.M112.422238. Epub 2012 Dec 3.

[2]. D'Arcy P,Brnjic S,Olofsson MH., et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med.2011 Nov 6;17(12):1636-40. doi: 10.1038/nm.2536.

质量控制

化学结构

NSC 687852