PDK1 inhibitor
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
PDK1抑制剂是有效的PDK1选择性抑制剂,可作为潜在的抗癌药物。GSK 2334470是PDK1抑制剂,对PDK1和CHEMBL1172241的IC50值分别为0.00251 M和0.085 M[1]。
PDPK1全称为3-磷酸肌醇依赖性蛋白激酶1,参与AKT/PKB以及多种其它AGC激酶激活,包括PKC、S6K和SGK[2]。PDPK1在多种生长因子与激素(包括胰岛素信号)激活的信号通路中起着重要作用。PDPK1与膜磷脂相互作用,从而作用于PI3K下游[3]。PI3K通过磷酸化磷脂酰肌醇,从而合成3,4-二磷酸磷脂酰肌醇和3,4,5-三磷酸磷脂酰肌醇以间接调节PDPK1[4]。然而,PDPK1具有组成型活性,不一定总需要磷脂酰肌醇。只有细胞膜上某些底物(包括AKT)的激活需要磷脂酰肌醇,而PDPK1不需要通过结合膜脂来磷酸化细胞质中的大多数底物。PDK1参与黑色素瘤发生发展过程[5]。许多致癌突变诱导PDK1靶标活化,包括Akt、S6K(p70核糖体S6激酶)和SGK(血清和糖皮质激素诱导的蛋白激酶)。
GSK2334470更有效抑制在细胞溶质中(相对于质膜上)被激活的PDK1底物。同样,在PDK1突变体敲入的胚胎干细胞中,免疫印迹测得其与磷酸肌醇的作用不如野生型细胞,而GSK2334470可以抑制Akt活化[6]。GSK2334470也抑制RSK2(p90核糖体S6激酶2)的T型环磷酸化及活化,而RSK2是另一个PDK1靶点,被ERK(细胞外信号调节激酶)通路所激活[7]。GSK2334470用于探讨PDK1相关的生理过程。因此,GSK2334470比其它已报道的PDK1抑制剂具有更特异的作用。
参考文献:
1. MurphyST. et al. Discovery of novel, potent, and selective inhibitors of 3-phosphoinositide-dependent kinase (PDK1). J Med Chem. 2011, 54(24):8490-500.
2. Mora A, Komander D, van Aalten DM, Alessi DR. "PDK1, the master regulator of AGC kinase signal transduction". Semin. Cell Dev. Biol. 2004,15 (2): 161-70.
3. Vanhaesebroeck B, Alessi DR. "The PI3K-PDK1 connection: more than just a road to PKB". Biochem. J. 2000, 346 (3): 561-76.
4. Frdin M, Antal TL. Et al. "A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation". EMBO J. 2002, 21 (20): 5396-407.
5. Scortegagna, M.. et al. "Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of BrafV600E::Pten-/- melanoma". Oncogene.2013.
6. Ayaz NAJAFOV. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem. J. (2011) 433, 357-369.
7. Tamguney, T. et al. Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells. Cell ,2008, 314, 2299–2312.
Storage | Store at -20°C |
M.Wt | 516.5 |
Cas No. | 1001409-50-2 |
Formula | C28H22F2N4O4 |
Solubility | Soluble in DMSO |
Chemical Name | 1-[(3,4-difluorophenyl)methyl]-2-oxo-N-[(1R)-2-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)oxy]-1-phenylethyl]pyridine-3-carboxamide |
SDF | Download SDF |
Canonical SMILES | C1=CC=C(C=C1)C(COC2=CC3=C(C=C2)NC(=O)N3)NC(=O)C4=CC=CN(C4=O)CC5=CC(=C(C=C5)F)F |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
Description | PDK1抑制剂是有效的PDK1选择性抑制剂,可作为潜在的抗癌药物。 | |||||
靶点 | PDK1 | |||||
IC50 |