pdk

PDK4-IN-1 hydrochloride, an anthraquinone derivative, is a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with an IC50 value of 84 nM.

PDK1-IN-RS2 inhibits the activation of the downstream kinases S6K1 by PDK1. PDK1-IN-RS2 is a mimic of the peptide docking motif (PIFtide) and is a substrate-selective PDK1 inhibitor (Kd: 9 μM).

MP7 (PDK1 inhibitor) is an inhibitor of phosphoinositide-dependent kinase-1 (PDK1).

PDK4-IN-1, an anthraquinone derivative, is a potent and orally active inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with an IC50 value of 84 nM.

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

Dehydroabiethylamine (NSC-2955) is an inducer of hepatic CYP2B activity. Dehydroabiethylamine inhibits pyruvate dehydrogenase kinases (PDKs) and intracellular cholesterol transport with anti-tumor activity.

Sodium dichloroacetate (BCA) , 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 a mitochondrial potassium-ion channel axis, trigger apoptosis in cancer cells, and inhibit tumor growth.

PS-47(PS 47) is an inactive E-isomer of PS48. PS48 is an activator of PDK1.

KPLH1130, a specific pyruvate dehydrogenase kinase (PDK) inhibitor, enhances glucose tolerance in mice fed a high-fat diet (HFD). It effectively hinders macrophage polarization and mitigates proinflammatory reactions.

PS210 is a potent and selective activator of PDK1 (Kd: 3 μM), specifically targeting the PIF-binding pocket of PDK1 without affecting other protein kinases such as S6K, PKB/Akt, or GSK3. Its prodrug, PS423, serves as a substrate-selective inhibitor of PDK1 in cells, inhibiting the phosphorylation and activation of S6K.

VER-246608 is an effective and ATP-competitive inhibitor of pyruvate dehydrogenase kinase (IC50s: 35 nM, 40 nM, 84 nM, and 91 nM for PDK-1, PDK-3, PDK-2, and PDK-4, respectively).VER-246608 disrupts Warburg metabolism and induces context-dependent cytosta

BX795 is an effective and selective PDK1 inhibitor (IC50: 6 nM), and its selectivity is 140- and 1600-fold for PDK1 over PKA and PKC in cell-free assays, respectively. Meanwhile, the selectivity for PDK1 is 100-fold than GSK3β.

BX-912 is a specific inhibitor of 3-Phosphoinositide-dependent Kinase-1 (PDK1, IC50: 12 nM). The selectivity of BX-912 is more 10 fold than C-Kit, EGFR, PKA, PKC etc.

JX06, a potent, selective and covalent PDK inhibitor, inhibits PDK1, PDK2 and PDK3 with IC50 of 49 nM, 101 nM and 313 nM respectively.

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

BX517 (PDK1 inhibitor 2) is a potent and selective inhibitor of PDK1.

δ-Tocotrienol (Delta-Tocotrienol) is a potential angiogenic inhibitor. δ-Tocotrienol is also a nontoxic activator of mir-34a which can inhibit nonsmall cell lung cancer cells (NSC-LC) cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.

RS1-PDK1 inhibitor (RS 1) is a selective inhibitor of the protein kinase PDK1 that can be used to treat and prevent disease or disorders.

PKM2/PDK1-IN-1, a shikonin thioether derivative, serves as a dual inhibitor for PKM2/PDK1. This compound effectively inhibits the proliferation and induces apoptosis in NSCLC cells. It promotes intercellular ROS production and modulates apoptotic proteins, engaging in both mitochondrial and death receptor pathways [1].

PDK-IN-3 (compound 1) is a potent pan-inhibitor of PDK, with IC50 values of 109.3 nM, 135.8 nM, 458.7 nM, and 8.67 μM for PDK 1-4, respectively. Additionally, PDK-IN-3 induces proliferation and apoptosis in A549 cells.

PDK-IN-1 (compound 7o), a pyruvate dehydrogenase kinase (PDK) inhibitor, exhibits IC50 values of 0.03 and 0.1 μM against PDK1 and HSP90, respectively. This compound effectively targets the PDH/PDK axis, significantly reducing tumor mass [1].

PDK-IN-2 (Compound 1F), with an IC50 of 68 nM, is a potent PDK inhibitor that downregulates the expression of PDK1 and PDK4 in cells. It promotes mitochondrial bioenergetics, reduces glycolytic activity, and triggers apoptosis via the mitochondrial pathway. Additionally, PDK-IN-2 has been shown to impede tumor growth in a 4T1 syngeneic mouse model [1].

LDHA/PDKs-IN-2 (compound 20k) is a potent dual inhibitor of LDHA and PDKs, with IC50 values of 0.7 and 1.6 μM, respectively. It increases oxygen consumption, decreases lactate formation, and shows potential for cancer research by reducing the proliferation of A549 cells with an EC50 of 15.7 μM [1].

LDHA/PDKs-IN-1 (compound 20e) is a highly effective dual inhibitor of PDKs and LDHA, with IC50 values of 0.8 μM and 0.15 μM, respectively. It significantly suppresses A549 cell proliferation (EC50 = 13.2 μM), reduces lactate formation, and enhances oxygen consumption, holding great promise for cancer research [1].