Among the downstream effectors of PI3Ks (see also section of PI3K/Akt/mTOR signaling), 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1; EC and protein kinase B (PKB)/Akt have a key role in several cancer types. There is evidence that indicates that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer, suggesting that inhibition of PDK1 can inhibit breast cancer progression[1]. PDK1 is the protein kinase responsible for regulating the activity of related kinases in the AGC kinase family (including AKT), by phosphorylating a specific threonine or serine residue within the activation loop (T-loop) which is critical for kinase activation. Many of the kinases activated by PDK1 regulate cellular processes such as cell survival, differentiation, growth, and protein expression, in response to second messenger signals. Activation of PI3K by growth factor signaling results in the production of phosphatidylinositol 3,4-bisphosphate and PIP3, which colocalize AKT and PDK1 to the plasma membrane through interaction with their respective pleckstrin homology (PH) domains, thus allowing PDK1 to phosphorylate AKT in a PIP3-dependent manner. Binding of PIP3 to AKT also induces conformational changes that facilitate PDK1 phosphorylation[2].

[1] C. Raimondi, M. Falasca. Targeting PDK1 in cancer. Curr. Med. Chem. 2011, 18, 2763-2769.
[2] J.R. Medina. Selective 3-Phosphoinositide-Dependent Kinase 1 (PDK1) Inhibitors: Dissecting the Function and Pharmacology of PDK1. J. Med. Chem., 2013, 56, 2726-2737.

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Axon ID Name Description From price
1282 BAG 956 PI3K and PDPK1 inhibitor €95.00
1390 BX 795 PDPK1, TBK1 and IKK inhibitor €65.00
1130 BX 912 PDPK1 inhibitor €65.00
2525 OSU 03012 ATP competitive PDK-1 inhibitor reducing PAK/Akt phosphorylation and cell proliferation €95.00
2610 PDK1 inhibitor 2610 Dual PI3K/PDPK1 inhibitor; desmethyl analogue of Axon 1282 €125.00
1870 PHT 427 Inhibitor of Akt and PDPK1 €75.00
1664 PS 47 Negative control of PS 48 as an allosteric PDK1 activator €90.00
1659 PS 48 Allosteric activator of phosphoinositide-dependent protein kinase 1 (PDPK1) €80.00

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