PDK

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.

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.

Rabusertib (IC-83) is an inhibitor of the cell cycle checkpoint kinase 1 (chk1) with potential chemopotentiating activity. Rabusertib has been used in trials studying the treatment of Cancer, Solid Tumors, Advanced Cancer, Pancreatic Neoplasms, and Non-Small Cell Lung Cancer.

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

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.

GSK-7227, a novel compound representing a novel class of peroxisome proliferator-activated receptor delta (PPARδ) partial agonists, demonstrates potent partial agonistic activity by upregulating the expression of PPARδ target genes, specifically carnitine palmitoyltransferase 1a (CPT1a) and pyruvate dehydrogenase kinase 4 (PDK4), in cultured skeletal muscle cells, indicating its potential role in modulating skeletal muscle metabolism and energy homeostasis.

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.

PS423 (PS210AM) is a substrate-selective inhibitor of PDK1 and a selective PDK1 activator that inhibits the phosphorylation and activation of S6K, and is used in the study of endocrine and metabolic disorders.

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.

Osu03012 (AR-12) is an orally bioavailable, small-molecule, celecoxib-derived inhibitor of phosphoinositide-dependent kinase-1 (PDK1) with potential antineoplastic activity.

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

PS 48 has been shown to be a PKB Kinase (PDK1) activator (Kd: 10.3 μM). This compound selectively binds to the PIF-binding pocket of PKB Kinase (PDK1).

Dicoumarol (Dicumarol) is a hydroxycoumarin originally isolated from molding sweet-clover hay, with anticoagulant and vitamin K depletion activities. Dicoumarol is a competitive inhibitor of vitamin K epoxidereductase; thus, it inhibits vitamin K recycling and causes depletion of active vitamin K in blood. This prevents the formation of the active form of prothrombin and several other coagulant enzymes, and inhibits blood clotting.

PKD-IN-1 dihydrochloride is an inhibitor of PKD.

PS10 is a broad-spectrum PDK inhibitor that inhibits PDK2, PDK4, PDK1, and PDK3. It significantly increases pyruvate dehydrogenase complex activity, and is used in research on obesity and type 2 diabetes.

M77976 is a selective ATP-competitive inhibitor of pyruvate dehydrogenase kinase 4 (PDK4) with an inhibitory effect on PDK4, having an IC50 value of 648 μM. It is used for research related to obesity and diabetes.

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

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.

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.

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

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

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