Home PI3K/Akt/mTOR PDPK1 inhibitor GSK2334470 For research use only.

GSK2334470

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

GSK2334470 Chemical Structure

CAS No. 1227911-45-6

Purity & Quality Control

GSK2334470 Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation 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
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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 PDK1K465E/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
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.

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)

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


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In vivo
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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

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