For a PDK1 inhibitor, the substrate matters.

@article{Knight2011ForAP,
  title={For a PDK1 inhibitor, the substrate matters.},
  author={Zachary A. Knight},
  journal={The Biochemical journal},
  year={2011},
  volume={433 2},
  pages={
          e1-2
        }
}
  • Z. Knight
  • Published 15 January 2011
  • Biology
  • The Biochemical journal
More than 20 protein kinases are directly activated by 3-phosphoinositide-dependent kinase 1 (PDK1), which is a central component of the pathways that regulate cell growth, proliferation and survival. Despite the importance of PDK1 in cell signalling, highly selective PDK1 inhibitors have not been described. In this issue of the Biochemical Journal, Dario Alessi's group and their collaborators at GlaxoSmithKline report GSK2334470, a potent and selective PDK1 inhibitor. They show that this… 
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13 Citations
Background Citations
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Results Citations
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13 Citations

Citation Type

Citation Type

3-Phosphoinositide-Dependent protein Kinase-1 (PDK1) inhibitors: A review from patent literature
TLDR
The intent of this review is to update the reader on the recent patent literature covering applications published between June 2008 and September 2011 that report on PDK1 inhibitors.
Targeting PDK1 in cancer.
TLDR
Accumulating evidence demonstrates that PDK1 is a valid therapeutic target and suggests thatPDK1 inhibitors may be useful to prevent cancer progression and abnormal tissue dissemination.
Autophagy and 3‐Phosphoinositide‐Dependent Kinase 1 (PDK1)‐Related Kinome in Pagetic Osteoclasts
TLDR
A strong potential regulatory role for PDK1 is indicated in OC stimulatory pathways (Akt, ERK) and autophagy induction (via mTORC1), which may contribute to the OC phenotype in PDB.
Substrate-selective inhibitors that reprogram the activity of insulin-degrading enzyme
TLDR
Using a high-throughput screen for non-active-site ligands, potent and highly specific small-molecule inhibitors are discovered that alter IDE’s substrate selectivity and offer a blueprint for modulating other enzymes in a substrate-selective manner to unlock their therapeutic potential.
PDK1 Inhibitor GSK-470 Exhibits Potent Anticancer Activity in a Pheochromocytoma PC12 Cell Tumor Model via Akt/mTOR Pathway.
TLDR
GSK-470 exhibited potent anticancer activity in PC12 tumor-bearing mice and appeared to be mediated by inhibition of the Akt/mTOR pathway, providing new insights into the therapeutic effects of inhibiting PDK1 in treatment of malignant PCC.
PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells
PurposeAKT plays a pivotal role in the signal transduction of cancer cells. MK2206, an AKT inhibitor, has been shown to be an effective anti-cancer drug to a variety of cancer cell lines. However,…
Protein kinase Cδ oxidation contributes to ERK inactivation in lupus T cells.
TLDR
Results identify PKCδ as a link between oxidative stress and the T cell epigenetic modifications in lupus, which prevents its phosphorylation and contributes to the decreased ERK signaling in l upus T cells.
Erratum to: PDK1-mTOR signaling pathway inhibitors reduce cell proliferation in MK2206 resistant neuroblastoma cells
TLDR
This research presents a novel probabilistic approach to estimating the response of the immune system to laser-spot assisted, 3D image recognition.
Analysis of the expression of INSR and FOX Genes in Celiac Disease
TLDR
Results indicated that FOXO4 and INSR were expressed less in celiac disease than normal non-celiac mucosa, and further studies will be needed to confirm if these findings are a result of the intestinal inflammation in CD or if these genes are partly driving the disease itself.
Spatial Dynamics and the Mechanoresponse in CD4+ T Cell Activation
TLDR
The work in this dissertation highlights the spatial and temporal dynamics that regulate the initial coupling of CD28 with TCR signaling and also dissects the mechanical properties conferred by downstream effectors that are required to relay CD28 costimulation.
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References

SHOWING 1-10 OF 10 REFERENCES
Analysis of 3-phosphoinositide-dependent kinase-1 signaling and function in ES cells.
Characterization of GSK2334470, a novel and highly specific inhibitor of PDK1.
TLDR
The small molecule GSK2334470 is described, which 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 PDK2 at 500-fold higher concentrations, and is suggested to be a useful tool for delineating the roles ofPDK1 in biological processes.
The selectivity of protein kinase inhibitors: a further update.
TLDR
Harmine has been identified as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro and the results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes.
Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1*
TLDR
The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents.
The nuts and bolts of AGC protein kinases
TLDR
The AGC kinase subfamily of protein kinases contains 60 members, including PKA, PKG and PKC, and their mutation and/or dysregulation contributes to the pathogenesis of many human diseases, including cancer and diabetes.
3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro
Use of the pharmacological inhibitor BX795 to study the regulation and physiological roles of TBK1 and IkappaB kinase epsilon: a distinct upstream kinase mediates Ser-172 phosphorylation and activation.
TLDR
It is demonstrated that TBK1 and IKKepsilon control a feedback loop that limits their activation by LPS, poly(I:C) and IL-1alpha (but not tumor necrosis factor alpha) to prevent the hyperactivation of these enzymes.
Features of selective kinase inhibitors.
3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase
Hypomorphic Mutation of PDK1 Suppresses Tumorigenesis in PTEN+/− Mice