pdhk

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.

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.

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

AZD7545 is a potent PDHK inhibitor.

PDHK-IN-3 (compound 7) is a potent inhibitor of pyruvate dehydrogenase kinase (PDHK) with IC50 values of 0.21 μM for PDHK2 and 1.54 μM for PDHK4 [1].

PDHK-IN-4 (Compound 30) is a potent inhibitor of PDHK, targeting PDHK2 (IC50: 0.0051 μM) and PDHK4 (IC50: 0.0122 μM), with potential applications in cancer research.

PDHK-IN-5 is a potent inhibitor of PDHK, acting on PDHK2 (IC50: 0.006 μM) and PDHK4 (IC50: 0.0329 μM), which are drug targets for many diseases including diabetes and cancer. PDHK-IN-5 has the potential to be investigated in cancer diseases.

PDHK-IN-7 (compound 32) acts as an inhibitor of pyruvate dehydrogenase kinase, exhibiting an IC50 value of 17 nM. Additionally, it activates PDH in rat liver and demonstrates a glucose-lowering effect in Zucker obese rats.

PDHK1-IN-1 (compound 17) is a selective inhibitor of PDHK1 with an IC50 value of 1.5 μM, demonstrating anticancer properties. PDHK1 negatively regulates the pyruvate dehydrogenase complex (PDC), thereby restricting the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Overexpression of PDHK1 leads to increased reliance on glycolysis (Warburg effect). PDHK1-IN-1 inhibits phosphorylation at the PDHK1 recognition site PDC E1α Ser232 and also suppresses phosphorylation of Ser293.

PDHK1-IN-3 (Compound 29) is a selective inhibitor of PDHK1, demonstrating an IC50 of 0.028 μM for PDHK1 and an IC50 of 0.120 μM for PDHK2. It inhibits PDHK1 activity by forming a covalent bond with Lys299 in the enzyme. PDHK1-IN-3 is applicable to research on autoimmune diseases, inflammatory conditions, and cancer.

PDHK1-IN-2 (Compound 24) is an ATP-competitive dual inhibitor of pyruvate dehydrogenase kinase 1/2 (PDHK1/2), with an IC50 of 0.007 μM for PDHK1 and 0.015 μM for PDHK2. PDHK1-IN-2 has the potential to regulate immune cell metabolism and correct mitochondrial dysfunction, making it a promising candidate for research in autoimmune diseases, inflammatory conditions, and cancer.

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.

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.

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

NG 52 (NG-52) is a cell-permeable, reversible, and ATP-compatible inhibitor of the cell cycle-regulating kinase Cdc28p and the related Pho85p kinase.

Dichloroacetate (DCA) is an inhibitor of all pyruvate dehydrogenase kinase (PDHK) isoforms, which are enzymes that phosphorylate and inhibit PDH in mitochondria. Inhibition of PDHK shifts cell metabolism from glycolysis to mitochondrial glucose oxidation, an effect that has relevance to cancer, type 2 diabetes, and other diseases. CAY10703 is a DCA trimer that is at least 10-fold more cytotoxic against leukemia cell lines than DCA. It is approximately 3-fold less cytotoxic than DCA against peripheral blood mononuclear cells from healthy blood donors. CAY10703 significantly reduces both basal and maximal respiration in leukemia cells. It is stable in vivo after subcutaneous inoculation, remaining in circulation for more than five hours after injection.

TM-1 is a potent pyruvate dehydrogenase kinase (PDHK) inhibitor that inhibits the activity of PDHK1 (IC50: 2.97 μM) and PDHK2 (IC50: 5.2 μM). TM-1 blocks pyruvate dehydrogenase complex (PDHC) phosphorylation and inhibits cancer cell proliferation.