您好,欢迎来到试剂仪器网! [登录] [免费注册]
试剂仪器网
位置:首页 > 产品库 > Degrasyn
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Degrasyn
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Degrasyn图片
CAS NO:856243-80-6
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
WP1130
产品介绍
Degrasyn (WP1130) 是可渗透细胞的去泛素化酶(DUB)抑制剂,直接抑制USP9x,USP5,USP14和UCH37的DUB活性。 Degrasyn 减弱抗细胞凋亡蛋白Bcr-AblJAK2
生物活性

Degrasyn (WP1130) is a cell-permeabledeubiquitinase(DUB)inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37. Degrasyn has been shown to downregulate the antiapoptotic proteinsBcr-AblandJAK2.

IC50& Target

IC50: 1.8 μM (Bcr-Abl, in K562, BV-173 cells)[1]
Deubiquitinase[2]

体外研究
(In Vitro)

Degrasyn, a small molecule that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. Degrasyn is more effective in inducing apoptosis of myeloid and lymphoid tumor cells (IC500.5 to 2.5 μM) than normal CD34+hematopoietic precursors, dermal fibroblasts, or endothelial cells (IC50~5 to 10 μM). Degrasyn reduces Bcr/Abl protein levels through a unique mechanism that is not affected by mutations that interfere with imatinib mesylate binding. Degrasyn inhibits phosphorylation of both the wild-type and the T315I mutant Bcr/Abl proteins, as demonstrated by the rapid disappearance (within 1 hour) of phosphotyrosyl-Bcr/Abl in both BV173 and BV173R cells. Degrasyn-induced down-regulation of Bcr/Abl is accompanied by apoptosis of CML cells[1]. Treatment with Degrasyn yields an anti-proliferative effect across all cell lines tested in a dose-dependent manner. Notably, treatment with Degrasyn results in marked anti-proliferative activity and morphological changes in NCH644 and NCH421K glioma stem-like cells. Treatment with Degrasyn results in a dose-dependent and probably compensatory increase of Mcl-1 mRNA levels after 6 h and only a minor decrease after 24 h. Similar findings are observed for Usp9X levels. These data suggest that Degrasyn down-regulates Mcl-1 and Usp9X through a post-transcriptional mechanism[2].

体内研究
(In Vivo)

Degrasyn suppresses the growth of K562 heterotransplanted tumors as well as both wild-type Bcr/Abl and T315I mutant Bcr/Abl-expressing BaF/3 cells transplanted into nude mice. To assess the possible therapeutic activity of Degrasyn against CML, nude mice received a subcutaneous transplant with K562 cells and are treated with 30 mg/kg Degrasyn every other day for 9 days after palpable tumor formation (10 days). This dose and schedule are well tolerated and effective in other tumor models. Antitumor activity is compared with that after daily Imatinib mesylate treatment (50 mg/kg). Nineteen days after tumor inoculation, tumors in the control group reached maximum allowable dimension, and the effect of therapy is assessed. Degrasyn treatment suppresses K562 tumor growth to an extent comparable to that observed in imatinib mesylate-treated animals, suggesting that Degrasyn is active in reducing the growth of established K562 tumors[1].

分子量

384.27

性状

Solid

Formula

C19H18BrN3O

CAS 号

856243-80-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : 100 mg/mL(260.23 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.6023 mL13.0117 mL26.0234 mL
5 mM0.5205 mL2.6023 mL5.2047 mL
10 mM0.2602 mL1.3012 mL2.6023 mL
*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 储存时,请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40%PEG300   5%Tween-80   45% saline

    Solubility: ≥ 2.5 mg/mL (6.51 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.51 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH2O 中,得到澄清透明的生理盐水溶液
  • 2.

    请依序添加每种溶剂: 10% DMSO    90%corn oil

    Solubility: ≥ 2.5 mg/mL (6.51 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (6.51 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在本网站选购。