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TPCA-1

现货
Catalog No.
A4602
IKK-2抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 800.00
现货
5mg
¥ 700.00
现货
10mg
¥ 1,200.00
现货
100mg
¥ 4,800.00
现货

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Background

TPCA-1 is a novel, potent, and selective inhibitor of human IKK-2.

Demonstration that IκB kinase 2 (IKK-2) plays a pivotal role in the nuclear factor-κB-regulated production of proinflammatory molecules by stimuli such as tumor necrosis factor (TNF)-α and interleukin (IL)-1 suggests that inhibition of IKK-2 may be beneficial in the treatment of rheumatoid arthritis.

In vitro: Determination of the activity of TPCA-1 against ten selected kinases, COX-1 and COX-2, showed the compound to be ~550-fold selective for IKK-2 versus ten of these enzymes. TPCA-1 inhibits lipopolysaccharide-induced human monocyte production of TNF-α, IL-6, and IL-8 with an IC50 of 170 to 320 nM [1].

In vivo: Prophylactic administration of TPCA-1 at 3, 10, or 20 mg/kg resulted in a dose dependent reduction in the severity of murine collagen-induced arthritis. The significantly reduced disease severity and delay of disease onset resulting from administration of TPCA-1 at 10 mg/kg were comparable to the effects of the antirheumatic drug, etanercept [1].

Clinical trial: No clinical data are available currently.

Reference:
[1] Podolin PL, Callahan JF, Bolognese BJ, Li YH, Carlson K, Davis TG, Mellor GW, Evans C, Roshak AK.  Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3 -thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation. J Pharmacol Exp Ther. 2005 Jan;312(1):373-81.

文献引用

1. Robert J. Posont. "The Role of Inflammatory Pathways in Development, Growth, and Metabolism of Skeletal Muscle in IUGR Offspring; Blood Gene Expression of Inflammatory Factors as Novel Biomarkers for Assessing Stress and Wellbeing in Exotic Species." University of Nebraska-Lincoln. 2019.
2. Robeson AC, Lindblom KR, et al. "Dimer-specific immunoprecipitation of active caspase-2 identifies TRAF proteins as novel activators." EMBO J. 2018 Jun 6. pii: e97072. PMID:29875129
3. Kwon Y, Choi SK, et al. "Involvement of inhibitor kappa B kinase 2 (IKK2) in the regulation of vascular tone." Lab Invest. 2018 May 21. PMID:29785049

Chemical Properties

Physical AppearanceA solid
StorageDesiccate at -20°C
M.Wt279.29
Cas No.507475-17-4
FormulaC12H10FN3O2S
Solubility≥13.95mg/mL in DMSO, ≥2.53 mg/mL in EtOH with ultrasonic and warming, <2.46 mg/mL in H2O
Chemical Name2-(carbamoylamino)-5-(4-fluorophenyl)thiophene-3-carboxamide
SDFDownload SDF
Canonical SMILESC1=CC(=CC=C1C2=CC(=C(S2)NC(=O)N)C(=O)N)F
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

人类单核细胞

溶解方法

在DMSO中的溶解度>14mg/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

0.1, 0.3, 1, 3和10 μM; 30 min

应用

在人外周血单核细胞中,TPCA-1以浓度依赖性方式抑制由LPS诱导的TNF-α,IL-6和IL-8的产生,IC50值分别为170,290和320nM。

动物实验[1]:

动物模型

胶原免疫/增强的DBA/1小鼠

剂量

3, 10或20 mg/kg, 腹腔注射, 每日2次,从第1天到第48天

应用

在胶原免疫/增强的DBA / 1小鼠中,TPCA-1(20或10mg / kg)剂量依赖性地降低关节炎的严重性,导致平均临床评分显著降低并延迟发病时间。TPCA-1(10mg / kg,腹腔注射,每日2次)也抑制p65核定位和IL-1β、IL-6、TNF-α和IFN-γ的爪组织水平。

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] Podolin PL, Callahan JF, Bolognese BJ, Li YH, Carlson K, Davis TG, Mellor GW, Evans C, Roshak AK. Attenuation of murine collagen-induced arthritis by a novel, potent, selective small molecule inhibitor of IkappaB Kinase 2, TPCA-1 (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3 -thiophenecarboxamide), occurs via reduction of proinflammatory cytokines and antigen-induced T cell Proliferation. J Pharmacol Exp Ther. 2005 Jan;312(1):373-81.

生物活性

Description TPCA-1是一种IκB激酶-2的选择性抑制剂,对IKK-2和IKK-1的IC50值分别为17.9 nM和0.4 μM。
靶点 IKK-2 IKK-1        
IC50 17.9 nM 0.4 μM        

质量控制

化学结构

TPCA-1

相关生物数据

TPCA-1

Related Biological Data

TPCA-1

Related Biological Data

TPCA-1

Related Biological Data

TPCA-1