切换导航

PD184352 (CI-1040)

现货
Catalog No.
A1792
MEK的选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
5mg
¥ 500.00
现货
25mg
¥ 1,800.00
现货
100mg
¥ 4,700.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

PD184352 (also known as CI-1040), a benzhydroxamate derivative, is a potent and highly selective MEK1/2, two members of the family of MAPKKs, inhibitor that inhibits purified MEK1 with IC50 of 17 nM in a non-ATP and non-ERK1/2 competitive manner [1].

PD184352 binds to a hydrophobic pocket, which is located in a region with low sequence homology to other kinases, adjacent to the Mg-ATP binding site of MEK1 and MEK2 inducing a conformational change in un-phosphorylated MEK1/2 and hence inactivating the un-phosphorylated MEK1/2 [1].

PD184352 has been found to be actively against tumors, where it inhibits the growth of colon carcinomas in mouse xenograft models [1].

References:
[1] Frémin C, Meloche S. From basic research to clinical development of MEK1/2 inhibitors for cancer therapy. J Hematol Oncol. 2010 Feb 11;3:8. doi: 10.1186/1756-8722-3-8.

文献引用

1. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt478.67
Cas No.212631-79-3
FormulaC17H14ClF2IN2O2
Solubility≥47.9mg/mL in DMSO
Chemical Name2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
SDFDownload SDF
Canonical SMILESC1CC1CONC(=O)C2=C(C(=C(C=C2)F)F)NC3=C(C=C(C=C3)I)Cl
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

表达FLAG-ERK5的CCl39细胞

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃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℃可放置数月。

反应条件

IC50: < 1 μM, 90 min

实验结果

将细胞在不含血清的培养基中培养16小时,随后加入PD184352或等量的DMSO处理90分钟,然后用10%FBS刺激单皿细胞15分钟,并用髓磷脂碱性蛋白(MBP;ERK1)或GST-MEF2C(ERK5)作为底物进行免疫复合物激酶测定。PD184352抑制FBS诱导的ERK1激活,IC50低于1 μM。从同一细胞提取物中,与ERK1以相同的方式诱导及实验,20 μM PD184352不足以抑制ERK5活性。

动物实验[2]:

动物模型

DBA/2-pcy/pcy小鼠

剂量

口服给药,400 mg/kg,第一周每天给药,随后每隔两天给药,再给药六周。

实验结果

与对照组pcy小鼠相比,PD184352处理的pcy小鼠的体重轻微但显著低于对照组。PD184352治疗结束后,pcy小鼠的肾重量、肾重量与体重比、BP和血清肌酐水平也显著下降。PD184352处理的pcy小鼠的水摄入减少,尿渗透压增加。PD184352处理的pcy小鼠的囊性指数也显著低于对照组pcy小鼠。

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] SQUIRES M, NIXON P, COOK S. Cell-cycle arrest by PD184352 requires inhibition of extracellular signal-regulated kinases (ERK) 1/2 but not ERK5/BMK1. Biochem. J, 2002, 366: 673-680.

[2] Omori S, Hida M, Fujita H, et al. Extracellular signal–regulated kinase inhibition slows disease progression in mice with polycystic kidney disease. Journal of the American Society of Nephrology, 2006, 17(6): 1604-1614.

生物活性

描述 PD184352是MEK的选择性抑制剂,Ki值300 nM。
靶点 MEK          
IC50 300 nM (Ki)          

质量控制

化学结构

PD184352 (CI-1040)