pyruvate dehydrogenase kinase

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.

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

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

AZD7545 is a potent PDHK inhibitor.

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.

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

FX-11 (LDHA Inhibitor FX11) is A potent, selective and competitive specific inhibitor of lactate dehydrogenase A (LDHA) with a Ki of 8 μM. FX-11 can activate PKM2 (pyruvate kinase M2). FX-11 can reduce ATP levels, induce oxidative stress and ROS production, and cause cell death. FX-11 appeared antitumor activity during xenotransplantation of lymphoma and pancreatic 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.

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.

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].

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.

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].

Mito-SilylDCA, a mitochondrial-targeted pyruvate dehydrogenase kinase (PDK1) inhibitor, possesses a thiamine pyrophosphate (TPP) moiety for PDK1 targeting within the mitochondrial network, several dichloroacetate (DCA) groups for effective PDK1 inhibition, a polyethylene glycol linker, and a silyl group [1].

PDK4-IN-2 (compound 8), a pyruvate dehydrogenase kinase 4 (PDK4) inhibitor, exhibits an inhibition concentration (IC 50) of 46 µM. By regulating bioenergetics and activating the tricarboxylic acid cycle [1], it enhances the ejection fraction in failing hearts.

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.