Aug 10, 2021 · We determined that DCA reduced the abundance of PDK1 in breast (MDA-MB-231) and prostate (PC-3) cancer cells, while it suppressed both PDK1 and PDK2 in skeletal muscle cells (L6 myotubes).

PDK1 expression was significantly associated with metastasis, reduced chemosensitivity, and poor overall and disease-free survival. Silencing of PDK1 retarded lactate production, cell adhesion, migration, invasion, and angiogenesis, and consequently metastasis.

Sep 6, 2017 · In this sense, dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, augments usage of the glycolysis-produced pyruvate in the mitochondria increasing oxidative phosphorylation...

Pyruvate dehydrogenase kinase 1 (PDK1) is a key factor in the connection between glycolysis and the tricarboxylic acid cycle. Restoring the mitochondrial OXPHOS function by inhibiting glycolysis through targeting PDK1 has become a hot spot for tumor therapy.

Nov 6, 2024 · PDK1 activates glycolysis to enhance stemness in hypoxia. To further explore whether PDK1 acts as a crucial regulator of BCSC maintenance by modulating glycolysis, we evaluated PDK1-positive cancer cell characteristics using a mouse xenograft tumor model.

Aug 14, 2018 · DCA, an inhibitor of PDKs, impedes glucose uptake and aerobic glycolysis in activated platelets. DCA inhibits agonist-induced human and mouse platelet aggregation and arterial thrombosis without altering hemostasis in mice.

Aug 14, 2007 · PDK1 crystals soaked with DCA produced unambiguous electron density for DCA in the F o − F c map of the PDK1-DCA complex (Figure 5A). The DCA-binding site is located inside the helix bundle in the N-terminal domain of PDK1 and is completely shielded from solvent in the apo-PDK1 structure.

Aug 14, 2018 · Mitochondrial pyruvate dehydrogenase kinases (PDK 1-4) play a pivotal role in metabolic flexibility by inhibiting pyruvate dehydrogenase complex. We determined whether metabolic reprogramming, diverting metabolism from aerobic glycolysis back to OXPHOS, would inhibit platelet function.

Jun 10, 2007 · We have determined structures of human PDK1 or PDK3 bound to the inhibitors AZD7545, dichloroacetate (DCA), and radicicol. We show that the trifluoromethylpropanamide end of AZD7545 projects into the lipoyl-binding pocket of PDK1.

Nov 29, 2012 · Oxamate, an LDH inhibitor, and dichloroacetate (DCA), a PDK1 inhibitor, were employed. Inhibition of PDK1 expression was achieved using a siRNA. High LDHA expression was found to be an indicator...