pdh

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.

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.

Devimistat (6,8-Bis(benzylthio)octanoic acid) , a lipoate analog, inhibits mitochondrial enzymes pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase, disrupts tumor cell mitochondrial metabolism. It has potential chemopreventive and antineoplastic activities, and has been used in trials studying the treatment of Cancer, Lymphoma, Solid Tumors, Advanced Cancer, and Pancreatic Cancer, among others.

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.

PDH E1-IN-1 is a selective TPP-competitive inhibitor of PDH E1 with an IC50 value of 0.99 μM.

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.

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

IMPDH2-IN-2 is a potent inhibitor of inosine 5'-monophosphate dehydrogenase (IMPDH) (Ki,app: 14 μM) and a potential anti-tuberculosis agent, exhibiting moderate antibacterial effects with MIC values of 6.3 and 11 μM in minimal GAST/Fe and rich 7H9/ADC/Tween media, respectively.

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.

SPDH is a cleavable antibody-drug conjugate (ADC) linker utilized for the diagnosis and therapy of cancer as well as B cell proliferative diseases.

IMPDH2-IN-4 (compound 2d) is a Mycophenolic acid analog and a selective IMPDH2 inhibitor with a Ki of 1.8 μM. It exhibits potent cytotoxic activity against osteosarcoma cancer cell lines. Additionally, IMPDH2-IN-4 demonstrates high affinity for VEGFR-2, CDK2, and IMPDH.

IMPDH-IN-1 (compound 44) functions as an inhibitor for the bacterial inosine monophosphate dehydrogenase (IMPDH). It specifically binds to the catalytic domain of IMPDH and effectively inhibits the IMPDH activity in organisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli.

GAPDH-IN-1 (Compound F8) is a GAPDH inhibitor, with an IC50 value of 39.31 μM for GAPDH enzyme activity. It forms a covalent adduct with the aspartic acid in the active site, displacing the enzyme's cofactor NAD+, and simultaneously enhances the reactivity of cysteine-reactive probes with the catalytic cysteine.

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.

IMPDHII/HDAC1-IN-1 (Compound C12) is an orally active dual inhibitor targeting IMPDHII and HDAC1, with IC50 values of 84.69 nM and 81.75 nM, respectively. It exhibits significant antitumor activity by inhibiting proliferation of K-562 cells (IC50 = 305.31 nM). By simultaneously targeting IMPDHII and HDAC1, this compound demonstrates a synergistic antitumor effect, suppressing tumor cell proliferation and inducing apoptosis. IMPDHII/HDAC1-IN-1 can be utilized in the study of cancers such as chronic myeloid leukemia (CML).

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.

TAT-PDHPS1 is a peptide inhibitor targeting Yes-associated protein (YAP) signaling, composed of the endogenous peptide PDHPS1 and the cell-penetrating peptide sequence TAT. It operates by binding to protein phosphatase 2 phosphatase activator (PTPA), thereby activating protein phosphatase 2A (PP2A). This activation precipitates the phosphorylation of YAP, culminating in the suppression of genes targeted by YAP. Demonstrated to inhibit the proliferation of ovarian cancer cells in vitro and reduce ovarian tumor growth in a subcutaneous xenograft mouse model, TAT-PDHPS1 presents a potent approach to managing ovarian malignancies.