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SW033291

现货
Catalog No.
A8709
15-PGDH酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 750.00
现货
25mg
¥ 2,700.00
现货

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Background

SW033291 is a potent inhibitor of 15-PGDH enzyme with IC50 value of 1.5 nM and dissociation constant Ki app value of 0.1 nM. SW033291 inhibits 15-PGDH with noncompetitive pattern. SW033291 shifted the 15-PGDH melting temperature by 13.5°C. [1]
Treatment of A549 cells with SW033291 increased PGE2 levels by 3.5-fold at 500 nM, with EC50 value of ~75 nM. In CD45 cells, SW033291 treatment induced a greater than four-fold increase in expression of CXCL12 and SCF. In SKL cells, SW033291 had no significant effects on expression of CXCL12, SCF, CXCR4, survivin, or JAG1. SW033291 also increased cyclic AMP levels in CD45 cells. SW033291 treatment increases the expression of cytokines from the hematopoietic niche. [1]
The phenotype of mice injected with SW033291 closely matched with 15-PGDH knockout mice (10mg/kg). SW033291 induced a two-fold increase in PGE2 levels in bone marrow, colon, lung, and liver. Importantly, no toxicity was induced by injecting SW033291 for inhibition of 15-PGDH in adult mice. Mice injected with SW033291 exhibited many good benefits, such as doubling peripheral neutrophils, a 65% increase in marrow SKL cells, a 71% increase in marrow SLAM cells, and 55% increases in the numbers of hematopoietic colonies. [1]
Reference:
1.    Zhang Y, Desai A, Yang SY et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240). pii: aaa2340.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt412.59
Cas No.459147-39-8
FormulaC21H20N2OS3
Solubility≥20.65mg/mL in DMSO
Chemical Name2-(butylsulfinyl)-4-phenyl-6-(thiophen-2-yl)thieno[2,3-b]pyridin-3-amine
SDFDownload SDF
Canonical SMILESNC1=C(S(CCCC)=O)SC2=NC(C3=CC=CS3)=CC(C4=CC=CC=C4)=C21
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

激酶实验 [1]:

重组15-PGDH蛋白活性测定

为了测定SW033291对15-PGDH酶活性的初始抑制特点,反应缓冲液 (50 mM Tris-HCl, pH7.5, 0.01% Tween 20) 包括了实验指定浓度的15-PGDH酶、实验指定浓度的SW033291、150 μM NAD(+)以及25 μM PGE2。在Envision Reader上,将反应混合物置于25°C下孵育15分钟。在加入PGE2后,立即测定于Ex/Em = 340 nM/485 nM波长下的荧光值,从而测定NADH的产生,每30秒测1次,持续3分钟,从而测定酶活性。使用GraphPad Prism 5软件,采用S形剂量效应曲线对SW033291浓度作图,计算IC50值。

细胞实验 [1]:

细胞系

CD45-骨髓细胞

制备方法

在DMSO中的溶解度大于20.7 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

0.5 μM;2小时

实验结果

在CD45-骨髓细胞中,SW033291抑制15-PGDH,增加PGE2的组织水平,并诱导CXCL12和SCF表达,从而加快移植的造血干细胞归巢、成熟血液组分产生,以及移植后正常血细胞计数恢复。 此外,抑制15-PGDH还能促进结肠或肝损伤后的细胞增殖,并加快上述组织修复。

动物实验 [1]:

动物模型

接受骨髓移植的小鼠和结肠和肝脏损伤小鼠模型

给药剂量

10 mg/kg;腹腔注射;每日2次

实验结果

在接受骨髓移植的小鼠中,SW033291促进造血恢复。在结肠和肝脏损伤小鼠模型中,SW033291降低结肠炎相关炎性细胞因子的水平,保护小鼠免受结肠炎,以及促进肝再生。

其它注意事项

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]. Zhang Y, Desai A, Yang SY et al. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015 Jun 12;348(6240). pii: aaa2340.

质量控制

化学结构

SW033291