Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer

In vitro evaluation of mitochondrial dysfunction and treatment with adeno-associated virus vector in fibroblasts from Doberman Pinschers with dilated cardiomyopathy and a pyruvate dehydrogenase kinase 4 mutation

(2016) Ivan Sosa et al.   AMERICAN JOURNAL OF VETERINARY RESEARCH

Mitochondria and Cancer

(2016) Sejal Vyas et al.   CELL

Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site

(2016) Tiziana Masini et al.   JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Unexpected Discovery of Dichloroacetate Derived Adenosine Triphosphate Competitors Targeting Pyruvate Dehydrogenase Kinase To Inhibit Cancer Proliferation

(2016) Shao-Lin Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis

(2016) Shih-Chin Cheng et al.   NATURE IMMUNOLOGY

Emerging concepts of T cell metabolism as a target of immunotherapy

(2016) Chih-Hao Chang et al.   NATURE IMMUNOLOGY

HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity

(2016) Hiroaki Semba et al.   Nature Communications

Honokiol bis-dichloroacetate (Honokiol DCA) demonstrates activity in vemurafenib-resistant melanoma in vivo

(2016) Michael Y. Bonner et al.   Oncotarget

Fundamentals of cancer metabolism

(2016) R. J. DeBerardinis et al.   Science Advances

Dichloroacetate induces cell cycle arrest in human glioblastoma cells persistently infected with measles virus: A way for controlling viral persistent infection

(2015) Megumi Takahashi et al.   ANTIVIRAL RESEARCH

Amino Acid Transporters in Cancer and Their Relevance to "Glutamine Addiction": Novel Targets for the Design of a New Class of Anticancer Drugs

(2015) Y. D. Bhutia et al.   CANCER RESEARCH

IDH1 Mutation Induces Reprogramming of Pyruvate Metabolism

(2015) J. L. Izquierdo-Garcia et al.   CANCER RESEARCH

A Lactate-Induced Response to Hypoxia

(2015) Dong Chul Lee et al.   CELL

Development of pyruvate dehydrogenase kinase inhibitors in medicinal chemistry with particular emphasis as anticancer agents

(2015) Shao-Lin Zhang et al.   DRUG DISCOVERY TODAY

Pyruvate dehydrogenase kinase expression and metabolic changes following dichloroacetate exposure in anoxic human colorectal cancer cells

(2015) Nelson Ho et al.   EXPERIMENTAL CELL RESEARCH

The pyruvate dehydrogenase complex in cancer: An old metabolic gatekeeper regulated by new pathways and pharmacological agents

(2015) Elise Saunier et al.   INTERNATIONAL JOURNAL OF CANCER

A phase I open-labeled, single-arm, dose-escalation, study of dichloroacetate (DCA) in patients with advanced solid tumors

(2015) Quincy Siu-Chung Chu et al.   INVESTIGATIONAL NEW DRUGS

Warburg-like Glycolysis and Lactate Shuttle in Mouse Decidua during Early Pregnancy

(2015) Ru-Juan Zuo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

In vivo analysis of lung cancer metabolism: nothing like the real thing

(2015) Christopher T. Hensley et al.   JOURNAL OF CLINICAL INVESTIGATION

Pyruvate carboxylase is critical for non–small-cell lung cancer proliferation

(2015) Katherine Sellers et al.   JOURNAL OF CLINICAL INVESTIGATION

Dual-targeting of aberrant glucose metabolism in glioblastoma

(2015) Han Shen et al.   JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH

Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate

(2015) Rosa Ferriero et al.   JOURNAL OF INHERITED METABOLIC DISEASE

Design, synthesis and anticancer activity of diam(m)ine platinum(II) complexes bearing a small-molecular cell apoptosis inducer dichloroacetate

(2015) Weiping Liu et al.   JOURNAL OF INORGANIC BIOCHEMISTRY

Design, Synthesis, and Biological Characterization of Novel Mitochondria Targeted Dichloroacetate-Loaded Compounds with Antileukemic Activity

(2015) Claudio Trapella et al.   JOURNAL OF MEDICINAL CHEMISTRY

Volumetric spiral chemical shift imaging of hyperpolarized [2-13c]pyruvate in a rat c6 glioma model

(2015) Jae Mo Park et al.   MAGNETIC RESONANCE IN MEDICINE

Dichloroacetate restores drug sensitivity in paclitaxel-resistant cells by inducing citric acid accumulation

(2015) Xiang Zhou et al.   Molecular Cancer

Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism

(2015) H. Shen et al.   MOLECULAR CANCER THERAPEUTICS

Fatty acid carbon is essential for dNTP synthesis in endothelial cells

(2015) Sandra Schoors et al.   NATURE

Silencing gastrin-releasing peptide receptor suppresses key regulators of aerobic glycolysis in neuroblastoma cells

(2015) Eric J. Rellinger et al.   PEDIATRIC BLOOD & CANCER

Dichloroacetate, the Pyruvate Dehydrogenase Complex and the Modulation of mESC Pluripotency

(2015) Ana Sofia Rodrigues et al.   PLoS One

Mitochondrial induction as a potential radio-sensitizer in lung cancer cells - a short report

(2015) Ronen Shavit et al.   CELLULAR ONCOLOGY

A potent tumoricidal co-drug ‘Bet-CA’ - an ester derivative of betulinic acid and dichloroacetate selectively and synergistically kills cancer cells

(2015) Suchandrima Saha et al.   Scientific Reports

Lactate Regulates Metabolic and Pro-inflammatory Circuits in Control of T Cell Migration and Effector Functions

(2015) Robert Haas et al.   PLOS BIOLOGY

VER-246608, a novel pan-isoform ATP competitive inhibitor of pyruvate dehydrogenase kinase, disrupts Warburg metabolism and induces context-dependent cytostasis in cancer cells

(2015) Jonathan D. Moore et al.   Oncotarget

Dichloroacetate blocks aerobic glycolytic adaptation to attenuated measles virus and promotes viral replication leading to enhanced oncolysis in glioblastoma

(2015) Chunyan Li et al.   Oncotarget

Mito-DCA: A Mitochondria Targeted Molecular Scaffold for Efficacious Delivery of Metabolic Modulator Dichloroacetate

(2014) Rakesh K. Pathak et al.   ACS Chemical Biology

Glycolytic enzyme upregulation and numbness of mitochondrial activity characterize the early phase of apoptosis in cerebellar granule cells

(2014) A. Bobba et al.   APOPTOSIS

Dichloroacetate affects proliferation but not survival of human colorectal cancer cells

(2014) L. M. Delaney et al.   APOPTOSIS

Modeling Alveolar Soft Part Sarcomagenesis in the Mouse: A Role for Lactate in the Tumor Microenvironment

(2014) Matthew L. Goodwin et al.   CANCER CELL

A Nuclear Pyruvate Dehydrogenase Complex Is Important for the Generation of Acetyl-CoA and Histone Acetylation

(2014) Gopinath Sutendra et al.   CELL

Sirtuin 4 Is a Lipoamidase Regulating Pyruvate Dehydrogenase Complex Activity

(2014) Rommel A. Mathias et al.   CELL

Druggable glycolytic requirement for Hedgehog-dependent neuronal and medulloblastoma growth

(2014) Laura Di Magno et al.   CELL CYCLE

The Right Ventricle in Pulmonary Arterial Hypertension

(2014) John J. Ryan et al.   CIRCULATION RESEARCH

From gametogenesis and stem cells to cancer: common metabolic themes

(2014) Sandro L. Pereira et al.   HUMAN REPRODUCTION UPDATE

Tyr-94 Phosphorylation Inhibits Pyruvate Dehydrogenase Phosphatase 1 and Promotes Tumor Growth

(2014) Changliang Shan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Inhibition of S6K1 enhances dichloroacetate-induced cell death

(2014) Sung-Eun Hong et al.   JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

Discovery and Optimization of 4,5-Diarylisoxazoles as Potent Dual Inhibitors of Pyruvate Dehydrogenase Kinase and Heat Shock Protein 90

(2014) Tao Meng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tyr Phosphorylation of PDP1 Toggles Recruitment between ACAT1 and SIRT3 to Regulate the Pyruvate Dehydrogenase Complex

(2014) Jun Fan et al.   MOLECULAR CELL

Combination of Taxol® and dichloroacetate results in synergistically inhibitory effects on Taxol-resistant oral cancer cells under hypoxia

(2014) QI XIE et al.   Molecular Medicine Reports

Dichloroacetate prevents restenosis in preclinical animal models of vessel injury

(2014) Tobias Deuse et al.   NATURE

Functional polarization of tumour-associated macrophages by tumour-derived lactic acid

(2014) Oscar R. Colegio et al.   NATURE

Local delivery of cancer-cell glycolytic inhibitors in high-grade glioma

(2014) Robert T. Wicks et al.   NEURO-ONCOLOGY

Pyruvate Induces Transient Tumor Hypoxia by Enhancing Mitochondrial Oxygen Consumption and Potentiates the Anti-Tumor Effect of a Hypoxia-Activated Prodrug TH-302

(2014) Yoichi Takakusagi et al.   PLoS One

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

(2014) Yufen Xie et al.   Stem Cell Research

Targeting Unique Metabolic Properties of Breast Tumor Initiating Cells

(2014) Weiguo Feng et al.   STEM CELLS

Myocardial Steatosis and Necrosis in Atria and Ventricles of Rats Given Pyruvate Dehydrogenase Kinase Inhibitors

(2014) Huw Bowen Jones et al.   TOXICOLOGIC PATHOLOGY

Nanoparticle Encapsulation of Mitaplatin and the Effect Thereof on In Vivo Properties

(2013) Timothy C. Johnstone et al.   ACS Nano

Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity

(2013) Toshimitsu Ohashi et al.   INTERNATIONAL JOURNAL OF CANCER

Phase 1 trial of dichloroacetate (DCA) in adults with recurrent malignant brain tumors

(2013) E. M. Dunbar et al.   INVESTIGATIONAL NEW DRUGS

Structure-guided Development of Specific Pyruvate Dehydrogenase Kinase Inhibitors Targeting the ATP-binding Pocket

(2013) Shih-Chia Tso et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Targeting lactate metabolism for cancer therapeutics

(2013) Joanne R. Doherty et al.   JOURNAL OF CLINICAL INVESTIGATION

SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways

(2013) Jeongsoon Park et al.   MOLECULAR CELL

Long-term safety of dichloroacetate in congenital lactic acidosis

(2013) Monica Abdelmalak et al.   MOLECULAR GENETICS AND METABOLISM

A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence

(2013) Joanna Kaplon et al.   NATURE

Metabolic response of glioma to dichloroacetate measured in vivo by hyperpolarized 13C magnetic resonance spectroscopic imaging

(2013) J. M. Park et al.   NEURO-ONCOLOGY

Wound Healing Improvement with PHD-2 Silenced Fibroblasts in Diabetic Mice

(2013) Xiongliang Zhang et al.   PLoS One

HIF1α Modulates Cell Fate Reprogramming Through Early Glycolytic Shift and Upregulation of PDK1-3 and PKM2

(2013) Alessandro Prigione et al.   STEM CELLS

Clinical and Experimental Applications of Sodium Phenylbutyrate

(2013) Tommaso Iannitti et al.   Drugs in research & development

Lysine Succinylation Is a Frequently Occurring Modification in Prokaryotes and Eukaryotes and Extensively Overlaps with Acetylation

(2013) Brian T. Weinert et al.   Cell Reports

Regulation of Muscle Pyruvate Dehydrogenase Complex in Insulin Resistance: Effects of Exercise and Dichloroacetate

(2013) Dumitru Constantin-Teodosiu   Diabetes & Metabolism Journal

The pyruvate dehydrogenase complex as a therapeutic target for age-related diseases

(2012) Peter W. Stacpoole   AGING CELL

A 16-bp deletion in the caninePDK4gene is not associated with dilated cardiomyopathy in a European cohort of Doberman Pinschers

(2012) Marta Owczarek-Lipska et al.   ANIMAL GENETICS

A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman pinscher

(2012) Kathryn M. Meurs et al.   HUMAN GENETICS

Comparison of Spheroids Formed by Rat Glioma Stem Cells and Neural Stem Cells Reveals Differences in Glucose Metabolism and Promising Therapeutic Applications

(2012) Marie Morfouace et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Multiple proteins with essential mitochondrial functions have glycosylated isoforms

(2012) Amanda R. Burnham-Marusich et al.   MITOCHONDRION

Glucose Oxidation Modulates Anoikis and Tumor Metastasis

(2012) S. Kamarajugadda et al.   MOLECULAR AND CELLULAR BIOLOGY

The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients

(2012) Kavi P. Patel et al.   MOLECULAR GENETICS AND METABOLISM

Mitaplatin Increases Sensitivity of Tumor Cells to Cisplatin by Inducing Mitochondrial Dysfunction

(2012) Xue Xue et al.   MOLECULAR PHARMACEUTICS

Metabolism of [U-13C]glucose in human brain tumorsin vivo

(2012) Elizabeth A. Maher et al.   NMR IN BIOMEDICINE

Signaling in Control of Cell Growth and Metabolism

(2012) P. S. Ward et al.   Cold Spring Harbor Perspectives in Biology

Transcriptional Regulation of Pyruvate Dehydrogenase Kinase

(2012) Ji Yun Jeong et al.   Diabetes & Metabolism Journal

Overexpression of Pyruvate Dehydrogenase Kinase 3 Increases Drug Resistance and Early Recurrence in Colon Cancer

(2011) Chun-Wun Lu et al.   AMERICAN JOURNAL OF PATHOLOGY

Development of a dichloroacetic acid-hemoglobin conjugate as a potential targeted anti-cancer therapeutic

(2011) Ning Zhang et al.   BIOTECHNOLOGY AND BIOENGINEERING

Lactate: A Metabolic Key Player in Cancer

(2011) F. Hirschhaeuser et al.   CANCER RESEARCH

Lactate Influx through the Endothelial Cell Monocarboxylate Transporter MCT1 Supports an NF- B/IL-8 Pathway that Drives Tumor Angiogenesis

(2011) F. Vegran et al.   CANCER RESEARCH

Somatic Oxidative Bioenergetics Transitions into Pluripotency-Dependent Glycolysis to Facilitate Nuclear Reprogramming

(2011) Clifford D.L. Folmes et al.   Cell Metabolism

Erk regulation of pyruvate dehydrogenase flux through PDK4 modulates cell proliferation

(2011) A. R. Grassian et al.   GENES & DEVELOPMENT

Human Polymorphisms in the Glutathione Transferase Zeta 1/Maleylacetoacetate Isomerase Gene Influence the Toxicokinetics of Dichloroacetate

(2011) Albert L. Shroads et al.   JOURNAL OF CLINICAL PHARMACOLOGY

Non-redox-active lipoate derivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo

(2011) Zuzana Zachar et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Hyperpolarized 13C magnetic resonance metabolic imaging: application to brain tumors

(2011) I. Park et al.   NEURO-ONCOLOGY

Oxygen Sensing, Homeostasis, and Disease

(2011) Gregg L. Semenza   NEW ENGLAND JOURNAL OF MEDICINE

Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate

(2011) E Babu et al.   ONCOGENE

A Locus on Chromosome 5 Is Associated with Dilated Cardiomyopathy in Doberman Pinschers

(2011) Theresa-Bernadette Mausberg et al.   PLoS One

Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1

(2010) Roel G.W. Verhaak et al.   CANCER CELL

Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs

(2010) Dirk Heshe et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Hypoxia-mediated biological control

(2010) Jessica Cassavaugh et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

The role of mitochondria in pulmonary vascular remodeling

(2010) Peter Dromparis et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Metabolic Modulation of Glioblastoma with Dichloroacetate

(2010) E. D. Michelakis et al.   Science Translational Medicine

Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling

(2010) Eric Verdin et al.   TRENDS IN BIOCHEMICAL SCIENCES

Calorie restriction alters mitochondrial protein acetylation

(2009) Bjoern Schwer et al.   AGING CELL

Hypoxia Enhances the Generation of Induced Pluripotent Stem Cells

(2009) Yoshinori Yoshida et al.   Cell Stem Cell

The anti-oxidant capacity of tumour glycolysis

(2009) Ulrike G. A. Sattler et al.   INTERNATIONAL JOURNAL OF RADIATION BIOLOGY

Subunit and Catalytic Component Stoichiometries of anin VitroReconstituted Human Pyruvate Dehydrogenase Complex

(2009) Chad A. Brautigam et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Pivotal Role of the C-terminal DW-motif in Mediating Inhibition of Pyruvate Dehydrogenase Kinase 2 by Dichloroacetate

(2009) Jun Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Interaction of E1 and E3 components with the core proteins of the human pyruvate dehydrogenase complex

(2009) Mulchand S. Patel et al.   JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC

Small mitochondria-targeting molecules as anti-cancer agents

(2009) Feng Wang et al.   MOLECULAR ASPECTS OF MEDICINE

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

(2009) Shanta Dhar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pyruvate into lactate and back: From the Warburg effect to symbiotic energy fuel exchange in cancer cells

(2009) Olivier Feron   RADIOTHERAPY AND ONCOLOGY

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

(2009) M. G. Vander Heiden et al.   SCIENCE

Comparative expression analysis of multiple PDK genes in Xenopus laevis during oogenesis, maturation, fertilization, and early embryogenesis

(2008) Alexander A. Tokmakov et al.   GENE EXPRESSION PATTERNS

Structural and Functional Insights into the Molecular Mechanisms Responsible for the Regulation of Pyruvate Dehydrogenase Kinase 2

(2008) Todd Green et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Pyruvate Dehydrogenase Kinase-4 Structures Reveal a Metastable Open Conformation Fostering Robust Core-free Basal Activity

(2008) R. Max Wynn et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Regulation of the PDK4 Isozyme by the Rb-E2F1 Complex

(2008) Michael C. F. Hsieh et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Evaluation of MR markers that predict survival in patients with newly diagnosed GBM prior to adjuvant therapy

(2008) Suja Saraswathy et al.   JOURNAL OF NEURO-ONCOLOGY

Evaluation of Long-term Treatment of Children With Congenital Lactic Acidosis With Dichloroacetate

(2008) P. W. Stacpoole et al.   PEDIATRICS

Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

(2008) Masato Kato et al.   STRUCTURE

Structures of the Human Pyruvate Dehydrogenase Complex Cores: A Highly Conserved Catalytic Center with Flexible N-Terminal Domains

(2008) Xuekui Yu et al.   STRUCTURE