Product Data SheetGSK2334470Cat. No.:CAS No.:Molecular Formula:Molecular Weight:Target:Pathway:Storage:HY-149811227911-45-6C₂₅H₃₄N₈O462.59PDK-1PI3K/Akt/mTORPowderIn solvent-20°C4°C-80°C-20°C3 years2 years6 months1 monthInhibitors•Agonists•Screening LibrariesSolvent & SolubilityIn Vitro10 mM in DMSOMass1 mg5 mg10 mgSolventConcentrationPreparing Stock Solutions1 mM5 mM10 mM2.1617 mL0.4323 mL0.2162 mL10.8087 mL2.1617 mL1.0809 mL21.6174 mL4.3235 mL2.1617 mLPlease refer to the solubility information to select the appropriate solvent.BIOLOGICAL ACTIVITYDescriptionIC₅₀ & TargetIn VitroGSK2334470 is a highly specific and potent inhibitor of PDK1 with an IC50 of 10 nM.IC50: 10 nM(PDK1)[1]Small molecule GSK2334470 inhibits PDK1 with an IC50 of ~10 nM, but does not suppress the activity of 93 other protein kinases including 13 AGC-kinases most related to PDK1 at 500-fold higher concentrations. Addition of GSK2334470 ablates T-loop residue phosphorylation and activation of SGK isoforms and S6K1 induced by serum or IGF-1 (insulin-like growth factor 1). GSK2334470 and AZD8055 effectively inhibite phosphorylation of PDK1 and mTOR, respectively, and induce higher G0–G1 ratio in LAN-1-MK than that in LAN-1 as well. PDK1 and mTOR inhibitors effecte on phosphorylation of GSK3β in some of resistant sublines[2].In VivoThe efficacy of the PDK1 inhibitor (PDKi) GSK2334470 is tested in newborn BrafV600E::Pten−/−mice subjected to systemic administration of 4-HT. Twice weekly administration of PDK1 results in marked inhibition of pigmented lesions and concomitant melanomagenesis, as well as significant inhibition of lung metastases, seen by H&E staining-1www.MedChemExpress.com
based quantification (~80%), and lymph node metastases as by S100 immunostaining, similar to the phenotype seen upon genetic ablation of Pdk1[3].
PROTOCOL
Cell Assay [2]
GSK2334470 is dissolved in DMSO and diluted with appropriate medium before use. To study the inhibitory effect of GSK2334470 on mTOR-S6K pathway, non-resistant cells and the resistant sublines are treated with GSK2334470 at 5 μM for 1.5 and 12 h in 10 % FBS medium with/without MK-2206 (5 μM)[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal
Administration [3]
Mice is dissolved in DMSO and then diluted with PBS or saline. BrafV600E::Pten−/− are generated as previously described. Cohorts of six animals per group are used in each experimental group. GSK2334470 is administered through IP injection (100 mg/kg) 3 times per week starting the same day of topical administration of 4-hydroxytamoxifen and ending at the time of mouse collection, based on earlier studies[3].MCE has not independently confirmed the accuracy of these methods. They are for reference only.
CUSTOMER VALIDATION
• Oncotarget. 2017 Jan 17;8(3):5003-5015.
See more customer validations on www.MedChemExpress.comREFERENCES
[1]. Najafov A, et al. Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1. Biochem J. 2011 Jan 15;433(2):357-69.
[2]. Qi L, et al. PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells. Cancer Cell Int. 2015 Sep 29;15:91.[3]. Scortegagna M, et al. Genetic inactivation or pharmacological inhibition of Pdk1 delays development and inhibits metastasis of Braf(V600E)::Pten(-/-) melanoma. Oncogene. 2014 Aug 21;33(34):4330-9.
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