Recent advances of mitochondrial complex I inhibitors for cancer therapy: Current status and future perspectives

Discovery and Lead Optimization of Benzene-1,4-disulfonamides as Oxidative Phosphorylation Inhibitors

(2022) Ding Xue et al.   JOURNAL OF MEDICINAL CHEMISTRY

Low-dose metformin targets the lysosomal AMPK pathway through PEN2

(2022) Teng Ma et al.   NATURE

Targeting OXPHOS and the electronic transport chain in cancer; Molecular and therapeutic implications

(2022) John Greene et al.   SEMINARS IN CANCER BIOLOGY

Identification of the Highly Active, Species Cross-Reactive Complex I Inhibitor BAY-179

(2022) Jeffrey Mowat et al.   ACS Medicinal Chemistry Letters

Combined inhibition of HMGCoA reductase and mitochondrial complex I induces tumor regression of BRAF inhibitor-resistant melanomas

(2022) Evelyn de Groot et al.   Cancer & Metabolism

Multiparameter Optimization of Oxidative Phosphorylation Inhibitors for the Treatment of Pancreatic Cancer

(2022) Ding Xue et al.   JOURNAL OF MEDICINAL CHEMISTRY

A novel anticancer pharmacological agent targeting mitochondrial complex I

(2022) Gabriela Reyes-Castellanos et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Mubritinib enhanced the inhibiting function of cisplatin in lung cancer by interfering with mitochondrial function

(2022) Jingyao Dong et al.   Thoracic Cancer

Properties of FDA-approved small molecule protein kinase inhibitors: A 2023 update

(2022) Robert Roskoski   PHARMACOLOGICAL RESEARCH

An Acidity‐Unlocked Nanoplatform Enables Self‐Boosting ROS Generation through Upregulation of Lactate for Highly Specific Chemodynamic Therapy

(2021) Linan Shi et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

NMS-873 functions as a dual inhibitor of mitochondrial oxidative phosphorylation

(2021) Miranda F. Bouwer et al.   BIOCHIMIE

SMAD4 loss limits the vulnerability of pancreatic cancer cells to complex I inhibition via promotion of mitophagy

(2021) Zuzana Ezrova et al.   ONCOGENE

First-in-human evaluation of the novel mitochondrial complex I inhibitor ASP4132 for treatment of cancer

(2021) Filip Janku et al.   INVESTIGATIONAL NEW DRUGS

Metformin: review of epidemiology and mechanisms of action in pancreatic cancer

(2021) Guido Eibl et al.   CANCER AND METASTASIS REVIEWS

Disrupting Mitochondrial Electron Transfer Chain Complex I Decreases Immune Checkpoints in Murine and Human Acute Myeloid Leukemic Cells

(2021) Raquel Luna-Yolba et al.   Cancers

Synchronous effects of targeted mitochondrial complex I inhibitors on tumor and immune cells abrogate melanoma progression

(2021) Mahmoud AbuEid et al.   iScience

Olaparib Is a Mitochondrial Complex I Inhibitor That Kills Temozolomide-Resistant Human Glioblastoma Cells

(2021) Luca X. Zampieri et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Mitochondrial complex I inhibitors suppress tumor growth through concomitant acidification of the intra- and extracellular environment

(2021) Junjiro Yoshida et al.   iScience

Glutaminase Inhibition Overcomes Acquired Resistance to Mitochondrial Complex I in NOTCH1-Driven T-Cell Acute Lymphoblastic Leukemias (T-ALL) Via Block of Glutamine Driven Reductive Metabolism

(2020) Natalia Baran et al.   BLOOD

Oxphos Inhibition Induces Formation of Tunneling Nanotubes in AML Cells and Facilitates Mitochondrial Transfer from BM Stroma to AML That Contributes to Microenvironment-Mediated Drug-Resistance of AML

(2020) Haeun Yang et al.   BLOOD

Rotenone restrains the proliferation, motility and epithelial–mesenchymal transition of colon cancer cells and the tumourigenesis in nude mice via PI3K/AKT pathway

(2020) Wusong Xue et al.   CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY

IACS-010759, a potent inhibitor of glycolysis-deficient hypoxic tumor cells, inhibits mitochondrial respiratory complex I through a unique mechanism

(2020) Atsuhito Tsuji et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase I study of IM156, a novel potent biguanide oxidative phosphorylation (OXPHOS) inhibitor, in patients with advanced solid tumors.

(2020) Sun Young Rha et al.   JOURNAL OF CLINICAL ONCOLOGY

Hydroxylated Rotenoids Selectively Inhibit the Proliferation of Prostate Cancer Cells

(2020) David A. Russell et al.   JOURNAL OF NATURAL PRODUCTS

Metformin selectively inhibits metastatic colorectal cancer with the KRAS mutation by intracellular accumulation through silencing MATE1

(2020) Jinye Xie et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Metabolic reprogramming and cancer progression

(2020) Brandon Faubert et al.   SCIENCE

Identification of a novel toxicophore in anti-cancer chemotherapeutics that targets mitochondrial respiratory complex I

(2020) Zoe A Stephenson et al.   eLife

Coordinate β-adrenergic inhibition of mitochondrial activity and angiogenesis arrest tumor growth

(2020) Cristina Nuevo-Tapioles et al.   Nature Communications

Inhibition of mitochondria NADH–Ubiquinone oxidoreductase (complex I) sensitizes the radioresistant glioma U87MG cells to radiation

(2020) Xingjie Gao et al.   BIOMEDICINE & PHARMACOTHERAPY

Differential regulation of mitochondrial complex I and oxidative stress based on metastatic potential of colorectal cancer cells

(2020) Neeraj Rai et al.   Oncology Letters

New insecticide screening platforms indicate that Mitochondrial Complex I inhibitors are susceptible to cross-resistance by mosquito P450s that metabolise pyrethroids

(2020) Rosemary S. Lees et al.   Scientific Reports

Identification of Mubritinib (TAK 165) as an inhibitor of KSHV driven primary effusion lymphoma via disruption of mitochondrial OXPHOS metabolism

(2020) Abram Calderon et al.   Oncotarget

Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses

(2019) Ivana Kurelac et al.   Nature Communications

Cytotoxic selectivity and apoptosis induction of piericidin A contributes potentially to its insecticidal effect against Mythimna separata (Lepidoptera: Noctuidae) larvae

(2019) Solange Muhayimana et al.   PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY

Modulation of autophagy by the novel mitochondrial complex I inhibitor Authipyrin

(2019) Nadine Kaiser et al.   BIOORGANIC & MEDICINAL CHEMISTRY

In vitro effects of antipsychotics on mitochondrial respiration

(2019) Tereza Cikánková et al.   NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY

Metabolic reprogramming toward oxidative phosphorylation identifies a therapeutic target for mantle cell lymphoma

(2019) Liang Zhang et al.   Science Translational Medicine

Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate

(2019) Valentina Sica et al.   Cell Reports

Mubritinib Targets the Electron Transport Chain Complex I and Reveals the Landscape of OXPHOS Dependency in Acute Myeloid Leukemia

(2019) Irène Baccelli et al.   CANCER CELL

Mitochondrial complex I inhibitor deguelin induces metabolic reprogramming and sensitizes vemurafenib-resistant BRAF V600E mutation bearing metastatic melanoma cells

(2019) Evan L. Carpenter et al.   MOLECULAR CARCINOGENESIS

The Mitochondrion as an Emerging Therapeutic Target in Cancer

(2019) Katherine G. Roth et al.   TRENDS IN MOLECULAR MEDICINE

Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis

(2019) Gang Cheng et al.   Nature Communications

Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus

(2019) Marc Foretz et al.   Nature Reviews Endocrinology

Mitochondrial Oxphos As Survival Mechanism of Minimal Residual AML Cells after Induction Chemotherapy : Survival Benefit By Complex I Inhibition with Iacs-010759

(2019) Lina Han et al.   BLOOD

Study protocol of a phase II clinical trial of oral metformin for the intravesical treatment of non-muscle invasive bladder cancer

(2019) Remco J. Molenaar et al.   BMC CANCER

Target Discovery of Selective Non-Small-Cell Lung Cancer Toxins Reveals Inhibitors of Mitochondrial Complex I

(2019) Nikhil Madhusudhan et al.   ACS Chemical Biology

Oxidative Phosphorylation as an Emerging Target in Cancer Therapy

(2018) Thomas M. Ashton et al.   CLINICAL CANCER RESEARCH

69P The diabetes drug canagliflozin sensitizes non-small cell lung cancer (NSCLC) to radiotherapy and chemotherapy

(2018) T. Tsakiridis et al.   Journal of Thoracic Oncology

An inhibitor of oxidative phosphorylation exploits cancer vulnerability

(2018) Jennifer R. Molina et al.   NATURE MEDICINE

Rotenone exerts developmental neurotoxicity in a human brain spheroid model

(2018) David Pamies et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Discovery of the novel autophagy inhibitor aumitin that targets mitochondrial complex I

(2018) Lucas Robke et al.   Chemical Science

Canagliflozin mediated dual inhibition of mitochondrial glutamate dehydrogenase and complex I: an off-target adverse effect

(2018) Philipp F. Secker et al.   Cell Death & Disease

Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity

(2018) Ana V. Coria-Téllez et al.   Arabian Journal of Chemistry

Mitochondrial Complex I Inhibitors Expose a Vulnerability for Selective Killing of Pten -Null Cells

(2018) Adam Naguib et al.   Cell Reports

Inhibition of Amino Acid Metabolism Selectively Targets Human Leukemia Stem Cells

(2018) Courtney L. Jones et al.   CANCER CELL

Stem cell-like breast cancer cells with acquired resistance to metformin are sensitive to inhibitors of NADH-dependent CtBP dimerization

(2018) Arindam Banerjee et al.   CARCINOGENESIS

Selective elimination of neuroblastoma cells by synergistic effect of Akt kinase inhibitor and tetrathiomolybdate

(2017) Jarmila Navrátilová et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres

(2017) Junseong Park et al.   NEURO-ONCOLOGY

Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I

(2017) Robin Krishnathas et al.   MedChemComm

Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells

(2017) Farhan Basit et al.   Cell Death & Disease

Mechanistic Investigations of the Mitochondrial Complex I Inhibitor Rotenone in the Context of Pharmacological and Safety Evaluation

(2017) Sabrina Heinz et al.   Scientific Reports

Current topics on inhibitors of respiratory complex I

(2016) Masatoshi Murai et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Structure and function of mitochondrial complex I

(2016) Christophe Wirth et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Unraveling the complexity of mitochondrial complex I assembly: A dynamic process

(2016) Laura Sánchez-Caballero et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

Mechanism of antineoplastic activity of lonidamine

(2016) Kavindra Nath et al.   BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER

Rotenone induces apoptosis in human lung cancer cells by regulating autophagic flux

(2016) Wensi Hu et al.   IUBMB LIFE

The unique chemistry and biology of the piericidins

(2016) Xuefeng Zhou et al.   JOURNAL OF ANTIBIOTICS

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation

(2016) Félix A. Urra et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Inhibiting stemness and invasive properties of glioblastoma tumorsphere by combined treatment with temozolomide and a newly designed biguanide (HL156A)

(2016) Junjeong Choi et al.   Oncotarget

The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

(2016) Linda A. Villani et al.   Molecular Metabolism

AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress

(2015) S. Sriskanthadevan et al.   BLOOD

Tumors and Mitochondrial Respiration: A Neglected Connection

(2015) Andrea Viale et al.   CANCER RESEARCH

Xanthohumol induces generation of reactive oxygen species and triggers apoptosis through inhibition of mitochondrial electron transfer chain complex I

(2015) Bo Zhang et al.   FREE RADICAL BIOLOGY AND MEDICINE

Inhibition of Mitochondrial Complex II by the Anticancer Agent Lonidamine

(2015) Lili Guo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Kalkitoxin Inhibits Angiogenesis, Disrupts Cellular Hypoxic Signaling, and Blocks Mitochondrial Electron Transport in Tumor Cells

(2015) J. Morgan et al.   Marine Drugs

A giant molecular proton pump: structure and mechanism of respiratory complex I

(2015) Leonid A. Sazanov   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Mitochondrial toxicity assessment in industry – a decade of technology development and insight

(2014) Yvonne Will et al.   Expert Opinion on Drug Metabolism & Toxicology

Molecular Mechanisms of Fenofibrate-Induced Metabolic Catastrophe and Glioblastoma Cell Death

(2014) Anna Wilk et al.   MOLECULAR AND CELLULAR BIOLOGY

Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function

(2014) Andrea Viale et al.   NATURE

Piericidin A Aggravates Tau Pathology in P301S Transgenic Mice

(2014) Matthias Höllerhage et al.   PLoS One

Mitochondrial inhibitor sensitizes non-small-cell lung carcinoma cells to TRAIL-induced apoptosis by reactive oxygen species and Bcl-XL/p53-mediated amplification mechanisms

(2014) Y-L Shi et al.   Cell Death & Disease

Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

(2014) William W Wheaton et al.   eLife

The role of mitochondrial electron transport in tumorigenesis and metastasis

(2013) An S. Tan et al.   BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

Inhibition of Lung Tumorigenesis by Metformin Is Associated with Decreased Plasma IGF-I and Diminished Receptor Tyrosine Kinase Signaling

(2013) B. J. Quinn et al.   Cancer Prevention Research

Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression

(2013) Antonio F. Santidrian et al.   JOURNAL OF CLINICAL INVESTIGATION

Exploiting the Role of Resveratrol in Rat Mitochondrial Permeability Transition

(2013) Yue Zhang et al.   JOURNAL OF MEMBRANE BIOLOGY

Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells

(2013) S Scotland et al.   LEUKEMIA

Suppression of Mitochondrial Complex I Influences Cell Metastatic Properties

(2013) Xuelian He et al.   PLoS One

Repositioning of Verrucosidin, a Purported Inhibitor of Chaperone Protein GRP78, as an Inhibitor of Mitochondrial Electron Transport Chain Complex I

(2013) Simmy Thomas et al.   PLoS One

Metformin Targets the Metabolic Achilles Heel of Human Pancreatic Cancer Stem Cells

(2013) Enza Lonardo et al.   PLoS One

Tumor cell death induced by the inhibition of mitochondrial electron transport: The effect of 3-hydroxybakuchiol

(2013) Fabián Jaña et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Relevance of Mitochondrial Genetics and Metabolism in Cancer Development

(2013) G. Gasparre et al.   Cold Spring Harbor Perspectives in Biology

BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I

(2013) Peter Ellinghaus et al.   Cancer Medicine

Abstract 4503: BAY 87-2243, an inhibitor of HIF-1α activation and stabilization, showed promising anti-tumor efficacy either as monotherapy or in combination with anti-VEGF and chemotherapy agents in preclinical tumor models

(2012) Kerstin Berhoerster et al.   CANCER RESEARCH

Abstract LB-244: BAY 87-2243, an inhibitor of HIF-1  - induced gene activation, showed promising anti-tumor efficacy in combination with anti-angiogenic therapy and irradiation in preclinical tumor models

(2012) H. Hess-Stumpp   CANCER RESEARCH

Metronomic Chemotherapy with the COMBAT Regimen in Advanced Pediatric Malignancies: A Multicenter Experience

(2012) D. Zapletalova et al.   ONCOLOGY

Investigating Metformin for Cancer Prevention and Treatment: The End of the Beginning

(2012) Michael N. Pollak   Cancer Discovery

Exploring Interactions between the 49 kDa and ND1 Subunits in Mitochondrial NADH-Ubiquinone Oxidoreductase (Complex I) by Photoaffinity Labeling

(2011) Masatoshi Murai et al.   BIOCHEMISTRY

Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

(2011) Guozhu Chen et al.   BMC CANCER

(+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo

(2011) G A S dos Santos et al.   LEUKEMIA

Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents

(2010) Aleem Gangjee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Metformin in Cancer Therapy: A New Perspective for an Old Antidiabetic Drug?

(2010) I. Ben Sahra et al.   MOLECULAR CANCER THERAPEUTICS

Autophagy and Metabolism

(2010) J. D. Rabinowitz et al.   SCIENCE

Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo

(2009) Ramon C. Sun et al.   BREAST CANCER RESEARCH AND TREATMENT

Natural lipophilic inhibitors of mitochondrial complex I are candidate toxins for sporadic neurodegenerative tau pathologies

(2009) Matthias Höllerhage et al.   EXPERIMENTAL NEUROLOGY

Rotenone induces apoptosis in MCF-7 human breast cancer cell-mediated ROS through JNK and p38 signaling

(2009) Yea-Tzy Deng et al.   MOLECULAR CARCINOGENESIS

How mitochondria produce reactive oxygen species

(2008) Michael P. Murphy   BIOCHEMICAL JOURNAL

Exploring the inhibitor binding pocket of respiratory complex I

(2008) Uta Fendel et al.   BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS

PPAR  agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition

(2008) D. Panigrahy et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Etoposide-resistant HT-29 human colon carcinoma cells during glucose deprivation are sensitive to piericidin A, a GRP78 down-regulator

(2007) Ji-Hwan Hwang et al.   JOURNAL OF CELLULAR PHYSIOLOGY

In Vivo Labeling of Mitochondrial Complex I (NADH:UbiquinoneOxidoreductase) in Rat Brain Using [3H]Dihydrorotenone

(2003) Deepa J. Talpade et al.   JOURNAL OF NEUROCHEMISTRY