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SB 203580

现货
Catalog No.
A8254
P38 MAP激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
25mg
¥ 630.00
现货
50mg
¥ 840.00
现货
100mg
¥ 1,460.00
现货
250mg
¥ 2,820.00
现货

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Background

SB203580, also called 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl) 1Himidazole [6], is a specific pyridinyl imidazole inhibitor of p38-MAPK (Mitogen-activated Protein Kinase) signaling pathway [1] [3]. It was competitive with ATP with a selectivity probably determined by nonconserved regions within or near the ATP binding pocket and a Ki of 21 nM [3]. It inhibits c-Raf with an IC50 of 2 mM in vitro [4].
p38 MAPK signaling pathway enables cells to generate a plethora of different effects to interpret a wide range of external signals and respond appropriately. There is a core of three protein kinases acting sequentially in this pathway to ensure the diversity and specificity in cellular outcomes [5].
Exposure to 30 mM SB203580 significantly decreased the resistance of L1210/VCR cells to vincristine accompanied by the LC50 value of vincristine changed from 3.2036±0.521 to 0.5576±0.082 mM. Exposure to 10 mM SB203580 slightly changed the value of the resistance index, accompanied by the LC50 values of SB203580 to sensitive L1210 cells and to resistant cells were 39.26±2.2 mM and 52.06±7.6 mM, respectively [1].
In vivo, administration of SB203580 alone 24 h before the permanent middle cerebral arterial occlusion abolished the isoflurane preconditioning-induced neuroprotection. After isoflurane exposure, administration of SB203580 decreased phosphorylated p38 MAPK. SB203580 inhibited anisomycin pretreatment-induced neuroprotection [6].
References:
[1]. Miroslav Baranclk, Vierka Bohacova, Janka Kvackajova, et al. SB203580, a specific inhibitor of p38-MAPK pathway, is a new reversal agent of P-glycoprotein-mediated multidrug resistance. European Journal of Pharmaceutical Sciences, 2001, 14: 29-36.
[2]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Molecular Pharmacology, 2004, 65:1172-1180.
[3]. Peter R. Young, Megan M. McLaughlin, Sanjay Kumar, et al. Pyridinyl Imidazole Inhibitors of p38 Mitogen-activated Protein Kinase Bind in the ATP Site. The Journal of Biological Chemistry, 1997, 272(18): 12116-12121.
[4]. Clare A Hall-Jackson, Michel Goedert, Philip Hedge, et al. E€ect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18: 2047-2054.
[5]. Ana Cuadrado and Angel R. Nebreda. Mechanisms and functions of p38 MAPK signalling. Biochem. J., 2010, 429: 403-417.
[6]. Shuqiu Zheng and Zhiyi Zuo. Isoflurane Preconditioning Induces Neuroprotection against Ischemia via Activation of P38 Mitogen-Activated Protein Kinases. Mol Pharmacol, 2004, 65: 1172-1180.

文献引用

Chemical Properties

StorageDesiccate at 4°C
M.Wt377.44
Cas No.152121-47-6
FormulaC21H16FN3OS
Solubility≥18.872mg/mL in DMSO, ≥3.28 mg/mL in EtOH with ultrasonic, <2.68 mg/mL in H2O
Chemical Name4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine
SDFDownload SDF
Canonical SMILESCS(=O)C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC=C(C=C4)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

Sf9细胞

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

IC50:2 μM

应用

在Sf9细胞中,编码v-Ras和Lck的DNA共转染可激活人c-Raf,其活性可直接用细胞裂解物测定或免疫沉淀之后测定。在Sf9细胞提取物中,SB 203580抑制c-Raf,IC50值为2 μM,比对SAPK2a/p38α的IC50值高40倍,但仅比SAPK2b/p38β2的IC50值高4倍。然而,在Sf9细胞、EGF刺激的小鼠Swiss 3T3细胞或EGF刺激的293细胞中,c-Raf免疫沉淀实验测得的IC50值要高10倍。

动物实验[2]:

动物模型

雌性Brown Norway大鼠

剂量

10-100 mg/kg;口服给药

应用

与对照组相比,SB 203580(10-100 mg/kg)口服给药对气道嗜酸粒细胞增多、BAL中性粒细胞增多和肺组织中嗜中性粒细胞基数均没有显著影响。BAL单核细胞/巨噬细胞的基数也不受SB 203580的影响(未挑战,对照组:443.8±36.2;挑战,对照组:414.1±29.7;挑战,SB 203580 100 mg/kg:381.5±41.8×103细胞/ml)。然而,SB 203580剂量相关地增加肺组织单核细胞/巨噬细胞的数量。

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] Hall-Jackson C A, Goedert M, Hedge P, et al. Effect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene, 1999, 18(12): 2047-2054.

[2] Escott K J, Belvisi M G, Birrell M A, et al. Effect of the p38 kinase inhibitor, SB 203580, on allergic airway inflammation in the rat. British journal of pharmacology, 2000, 131(2): 173-176.

生物活性

描述 SB203580是p38 MAPK的抑制剂,IC50范围介于0.3-0.5 μM之间,对SAPK3(106T)和SAPK4(106T)选择性低10倍,且阻断PKB磷酸化,IC50值为3-5 μM。
靶点 p38 MAPK PKB        
IC50 0.3–0.5 μM 3–5 μM        

质量控制

化学结构

SB 203580

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