pdhk1

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.

AZD7545 is a potent PDHK inhibitor.

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.

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.

PBS-1086 is a novel dual inhibitor of the canonical and noncanonical NF-κB pathways, increasing the magnitude and duration of initial EGFR inhibitor response in multiple NSCLC models, decreasing PDHK1 expression, and suppressing phosphorylation of the PDHK1 protein substrate PDHA1 in a panel of PTEN-deficient cell lines.