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GSK2334470

Name: GSK2334470
Brand: Selleck Chemicals
SKU: S7087
Rating: 5 (28 reviews)

Catalog No.S7087 Purity:99.96%

GSK2334470 is a novel PDK1 inhibitor with IC50 of ~10 nM in a cell-free assay, with no activity at other close related AGC-kinases.

GSK2334470 Chemical Structure

CAS No. 1227911-45-6

Purity & Quality Control

Batch: Purity: 99.96%

99.96

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Cell Data

Cell Lines	Assay Type	Activity Description	PMID
PC3 cells	Function assay	Inhibition of PDK1-mediated AKT phosphorylation at Thr308 residue in human PC3 cells by ELISA, IC50=0.113 μM	21341675
PC3 cells	Function assay	Inhibition of PDK1-mediated RSK phosphorylation at Ser221 residue in human PC3 cells by ELISA, IC50=0.293 μM	21341675
K562 cells	Proliferation assay	Antiproliferative activity against human K562 cells, IC50=18 μM	21341675
OCI-AML2 cells	Proliferation assay	Antiproliferative activity against human OCI-AML2 cells, IC50=0.35 μM	21341675
OCI-AML3 cells	Proliferation assay	Antiproliferative activity against human OCI-AML3 cells, IC50=0.52 μM	21341675
F-36P cells	Proliferation assay	Antiproliferative activity against human F-36P cells, IC50=0.28 μM	21341675
insect cells	Function assay	Inhibition of recombinant full length PDK1 (unknown origin) expressed in insect cells assessed as inhibition of Akt activation measured for 30 mins in presence of [gamma32P-ATP], IC50=0.01 μM	23448267
Click to View More Cell Line Experimental Data

Biological Activity

Description

GSK2334470 is a novel PDK1 inhibitor with IC50 of ~10 nM in a cell-free assay, with no activity at other close related AGC-kinases.

Targets

PDPK1 ^[1]
(Cell-free assay)

10 nM

In vitro
In vitro	GSK2334470 inhibits PDK1 from activating full-length Akt1 in the presence of PtdIns(3,4,5)P₃-containing lipid vesicles or a mutant of Akt1 lacking the PH domain (ΔPH-Akt1) with IC50 of ~10 nM. GSK2334470 also similarly inhibits PDK1 from phosphorylating the PDKtide peptide substrate with IC50 of ~10 nM. GSK2334470 (0.1 μM–0.3 μM) induces significant dose-dependent inhibition of endogenous NDRG1 with over 50% reduction in phosphorylation in HEK-293 cells. GSK2334470 (30 nM) induces a significant dose-dependent inhibition of the T-loop phosphorylation of each SGK isoform in HEK-293 cells. GSK2334470 (1 μM) inhibits hydrophobic motif phosphorylation of S6K1 to a similar extent as T-loop phosphorylation in HEK-293 cells. GSK2334470 (3 μM) also suppresses S6K1 activity and phosphorylation induced by IGF1 stimulation of serum-starved HEK-293 cells. GSK2334470 (3 μM) markedly inhibits the phosphorylation of several Akt substrates [FoxO (forkhead box O), GSK3 and PRAS40]. GSK2334470 (3 μM) also induces near maximal inhibition of Akt1 activity and phosphorylation within 5 min, and Akt substrate phosphorylation (FoxO, GSK3 and PRAS40) is inhibited at a slightly later time point (10 min). GSK2334470 (0.3 μM) significantly inhibits phosphorylation of Akt or PRAS40/GSK3 in PDK1K^465E/K465E knock-in but not wild-type ES cells. GSK2334470 (1 μM) effectively suppresses SGK1 activity as judged by the inhibition of NDRG1 phosphorylation in U87 glioblastoma cells. GSK2334470 (1 μM) also potently suppresses activation of S6K1 (Figure 7B) as well as SGK1 in MEF (mouse embryonic fibroblast) cells. GSK2334470 (0.1 μM) induces ~50% inhibition of RSK2 activity in HEK-293 cells. ^[1] GSK2334470 (30 µM) suppresses U46619 induced Ca²⁺-sensitized force in α-toxin permeabilized rabbit pulmonary artery SM. GSK2334470 (30 µM) results in a significant decrease in the contractile force in response to [Ca²⁺]. ^[2] GSK2334470 (1 μM) results in total abrogation of the EGF-induced intracellular calcium increase and inositol phosphates accumulation in MDA-MB-231 cells. GSK2334470 (1 μM) inhibits PLCγ1 Tyr783 phosphorylation in MDA-MB-231 cells. ^[3]
Kinase Assay	Kinase activity assays
Kinase Assay	Endogenous Akt, S6K and RSK are immunoprecipitated from 0.1 mg to 1 mg of cell lysate for 2 hours at 4℃ on a vibrating platform using 3 μg–5 μg of the indicated antibodies. For the SGK activity assays, 150 μg of transfected lysate is incubated with 5 μg of glutathione–Sepharose for 3 hours at 4℃. The immunoprecipitates are washed twice with lysis buffer containing 0.5 mM NaCl, followed by two washes with kinase buffer. Kinase reactions are initiated by a reaction mixture to bring the final concentrations of the reaction components to 0.1 mM [γ-³²P]ATP (~200 c.p.m./pmol), 5 mM magnesium acetate, 0.1% 2-mercaptoethanol and 30 mM Crosstide peptide (GRPRTSSFAEGKK). Reactions are carried out for 20 min at 30℃ on a vibrating platform and stopped by spotting the reactions on to P81 phosphocellulose paper. Cerenkov counting is done after washing the papers in phosphoric acid, rinsing in acetone and air-drying. One unit of activity is defined as that which catalysed the incorporation of 1 nmol of [³²P]phosphate into the substrate over 1 hour.
Cell Research	Cell lines	MDA-MB-231 cells
	Concentrations	1 µM
	Incubation Time	30 minutes
	Method	Cells were incubated with 1 µM of GSK2334470 for 30 minutes. Cells treated with DMSO were used as control.
Experimental Result Images	Methods	Biomarkers	Images	PMID
	Western blot	pRb / pPDK1 / pAKT / pRSK2 / p70S6K / pPRAS40 / pS6 p-Myc / Myc / p-p70 / p70		28249908
	Immunofluorescence	KDM4A / Pol-I		26729372

In Vivo
In vivo	GSK2334470 is a highly specific and potent inhibitor of PDK1.
Animal Research	Animal Models	Nude mice
	Dosages	100 mg/kg
	Administration	i.p.

References

[4] Scortegagna M, et al. Oncogene. 2014 Aug 21;33(34):4330-9.

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Chemical Information & Solubility

Molecular Weight	462.59	Formula	C₂₅H₃₄N₈O
CAS No.	1227911-45-6	SDF	Download GSK2334470 SDF
Smiles	CC1CCC(CN1C2=NC(=NC(=C2)C3=CC4=C(C=C3)C(=NN4)N)NC)C(=O)NC5CCCCC5
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 93 mg/mL ( (201.04 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 93 mg/mL

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.650mg/ml (10.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 93 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

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Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
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