PDK

PDK1 (Phosphoinositide-dependent kinase-1) also known as PDPK1 (3-phosphoinositide dependent protein kinase-1) is a serine/threonine protein kinase, which functions as a master kinase to phosphorylate and activate a subgroup of the AGC family kinases such as PKB/Akt, PKC, S6K, SGK, and RSK, thus, playing a pivotal role in the PI3K/Akt signaling pathway. [show the full text]

PI3K/Akt/mTOR

Aurora Kinase CDK Chk ROCK PLK Antimetabolites APC Wee1 MPS1 Rho Myc DYRK BMI-1 eIF LIM kinase PFKFB RUNX FOXM1 Choline kinase Haspin Kinase Mad2 p21 Cyclin CDK4/6 Cell Cycle Arrest

Isoform-selective Products

PDK1 PDK2 PDK3

All (4)
PDK Inhibitors (4)
New PDK Products

Cat.No.	Product Name	Information	Product Use Citations
S1274	BX-795	BX-795 is a potent and specific PDK1 inhibitor with IC50 of 6 nM, 140- and 1600-fold more selective for PDK1 than PKA and PKC in cell-free assays, respectively. Meanwhile, in comparison to GSK3β more than 100-fold selectivity observed for PDK1. BX-795 modulates autophagy via inhibiting ULK1. BX-795 also is a potent TBK1 inhibitor that blocks both TBK1 and IKKε with IC 50 values of 6 nM and 41 nM, respectively.	Cancer Res, 2025, 10.1158/0008-5472.CAN-25-1791 Cell Rep, 2025, 44(7):115972 EMBO J, 2024, 10.1038/s44318-024-00244-9
S0983	JX06	JX06 is a selective covalent inhibitor of PDK1 in cells. This compound dose-dependently inhibits PDK1, PDK2 and PDK3 with IC50 0.049 μM, 0.101 μM and 0.313 μM, respectively.	Biochem Biophys Res Commun, 2021, 587:153-159
S8615	Sodium Dichloroacetate (DCA)	DCA (Sodium dichloroacetate), a specific inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50 values of 183 and 80 μM for PDK2 and PDK4 respectively, has been shown to derepress Na⁺-K⁺-2Cl^- cotransporter and a mitochondrial potassium-ion channel axis. This compound increases reactive oxygen species (ROS) generation, triggers apoptosis in cancer cells, and inhibits tumor growth.	bioRxiv, 2025, 2025.04.03.647023 bioRxiv, 2025, 2025.08.24.671623 bioRxiv, 2025, 2023.08.11.552890
S2949	KPLH1130	KPLH1130 is a specific inhibitor of pyruvate dehydrogenase kinase (PDK) that blocks macrophage polarization and attenuates proinflammatory responses.
S1274	BX-795	BX-795 is a potent and specific PDK1 inhibitor with IC50 of 6 nM, 140- and 1600-fold more selective for PDK1 than PKA and PKC in cell-free assays, respectively. Meanwhile, in comparison to GSK3β more than 100-fold selectivity observed for PDK1. BX-795 modulates autophagy via inhibiting ULK1. BX-795 also is a potent TBK1 inhibitor that blocks both TBK1 and IKKε with IC 50 values of 6 nM and 41 nM, respectively.	Cancer Res, 2025, 10.1158/0008-5472.CAN-25-1791 Cell Rep, 2025, 44(7):115972 EMBO J, 2024, 10.1038/s44318-024-00244-9
S0983	JX06	JX06 is a selective covalent inhibitor of PDK1 in cells. This compound dose-dependently inhibits PDK1, PDK2 and PDK3 with IC50 0.049 μM, 0.101 μM and 0.313 μM, respectively.	Biochem Biophys Res Commun, 2021, 587:153-159
S8615	Sodium Dichloroacetate (DCA)	DCA (Sodium dichloroacetate), a specific inhibitor of pyruvate dehydrogenase kinase (PDK) with IC50 values of 183 and 80 μM for PDK2 and PDK4 respectively, has been shown to derepress Na⁺-K⁺-2Cl^- cotransporter and a mitochondrial potassium-ion channel axis. This compound increases reactive oxygen species (ROS) generation, triggers apoptosis in cancer cells, and inhibits tumor growth.	bioRxiv, 2025, 2025.04.03.647023 bioRxiv, 2025, 2025.08.24.671623 bioRxiv, 2025, 2023.08.11.552890
S2949	KPLH1130	KPLH1130 is a specific inhibitor of pyruvate dehydrogenase kinase (PDK) that blocks macrophage polarization and attenuates proinflammatory responses.

Signaling Pathway Map

PDK1 protein is composed of two well-characterized functional domains: (1) the N-terminal serine/threonine kinase domain of the AGC family, and (2) the C-terminal Pleckstrin homology (PH) domain that interacts with high affinity with both PtdIns(3,4,5)P3 and PtdIns(3,4)P2 as well as other phosphoinositides such as PtdIns(4,5)P2. PDK1 is ubiquitously expressed and constitutively active in mammalian cells. In addition to being able to constitutively phosphorylate substrates, PDK1 also works in an inducible manner in response to specific stimuli. Without stimuli, the catalytic activity of PDK1 is kept under control by limiting its access to targets, whereas upon stimulation, the different PDK1 substrates are converted into forms that can be recognized, phosphorylated and activated by PDK1. PDK1 regulates as much as 23 growth-factor-stimulated AGC kinases, containing protein kinase B (PKB/Akt) isoforms, p70 ribosomal protein S6 kinase (S6K) isoforms, p90 ribosomal protein S6 kinases (RSK), serum- and glucocorticoid-induced protein kinase (SGK) isoforms, and several protein kinase C (PKC) isoforms, by phosphorylating at the serine/threonine residues in their T-loop. ^[1]

The autophosphorylation of PDK1 at Ser241 in the T-loop or activation loop contributes to the catalytic activity of PDK1 upon substrate binding, and several other phosphorylation sites have also been proposed to contribute to the regulation of PDK1 activity. Upon growth factor stimulation and PtdIns(3,4,5)P3 production, both PKB/Akt and PDK1 translocate to the plasma membrane via the specific interaction of their PH domains with newly generated PtdIns(3,4,5)P3, where PDK1 could then readily phosphorylate and activate PKB/Akt, allowing PKB/Akt to phosphorylate downstream targets such as Foxo1. The mTORC1 or mTORC2 mediated phosphorylation of the hydrophobic motif of AGC kinases is essential for PDK1-mediated activation. This is achieved by creating a docking site for the binding of PDK1 to facilitate the phosphorylation of the kinases at its T-loop by PDK1. Moreover, the interaction of the hydrophobic motif binding pocket (PIF pocket) of PDK1 with the phosphorylated hydrophobic motif in the substrate induces the allosteric activation of PDK1. ^[1]

Therefore, through targeting a particular set of these AGC kinases, PDK1 play a critical role in regulating a wide variety of physiological processes including cell growth, proliferation, survival, development, and metabolism. PDK1 knockout mice die during early embryonic development, and the PDK1 dominant negative mutants knock-in mice are also shown to be embryonically lethal. A series of tissue-specific conditional knockout mice lacking PDK1 also confirm both the implication of PDK1 in mediating metabolic responses to insulin as well as in promoting cell viability, which proposes that selective activation of PDK1 might be a good strategy for the treatment of diabetes. However, PDK1 overexpression and amplification of the PDK1 gene are common occurrences in breast cancer and acute myeloid leukaemia. PDK1 also displays an epistatic relationship with the lipid phosphatase PTEN in the migration and malignant transformation of lymphocytes and in regulating nervous system development. Moreover, PTEN heterozygous mice expressing reduced levels of PDK1 are markedly protected from developing a wide range of tumors, indicating that PDK1 is a key effector in mediating tumorigenesis resulting from loss of PTEN and further validating PDK1 as a valuable anticancer target for the development of specific inhibitors. ^[1]