Recent advances of human dihydroorotate dehydrogenase inhibitors for cancer therapy: Current development and future perspectives

DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes

(2021) Kensuke Kayamori et al.   Blood Advances

Pharmacological review of isobavachalcone, a naturally occurring chalcone

(2021) Miaojuan Wang et al.   PHARMACOLOGICAL RESEARCH

SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation

(2021) Xuemei Qiu et al.   International Journal of Oral Science

The Synergism between DHODH Inhibitors and Dipyridamole Leads to Metabolic Lethality in Acute Myeloid Leukemia

(2021) Valentina Gaidano et al.   Cancers

Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold: SAR of the Biphenyl Moiety

(2021) Stefano Sainas et al.   JOURNAL OF MEDICINAL CHEMISTRY

DHODH-mediated ferroptosis defence is a targetable vulnerability in cancer

(2021) Chao Mao et al.   NATURE

Investigating dihydroorotate dehydrogenase inhibitor mediated mitochondrial dysfunction in hepatic in vitro models

(2021) Samantha W. Jones et al.   TOXICOLOGY IN VITRO

DHODH and cancer: promising prospects to be explored

(2021) Yue Zhou et al.   Cancer & Metabolism

Exploring Marine-Derived Ascochlorins as Novel Human Dihydroorotate Dehydrogenase Inhibitors for Treatment of Triple-Negative Breast Cancer

(2021) Xiaowei Luo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Nucleotide Metabolism

(2021) Navdeep S. Chandel   Cold Spring Harbor Perspectives in Biology

Combination of consensus and ensemble docking strategies for the discovery of human dihydroorotate dehydrogenase inhibitors

(2021) Garri Chilingaryan et al.   Scientific Reports

Identification of Dihydroorotate Dehydrogenase Inhibitors─Indoluidins─That Inhibit Cancer Cell Growth

(2021) Makoto Kawatani et al.   ACS Chemical Biology

Identification of De Novo Pyrimidine Synthesis as a Targetable Vulnerability in a Novel IDH1 Mutant Engineered Astrocytoma Model

(2021) D.D. Shi et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

Dihydroorotate dehydrogenase in oxidative phosphorylation and cancer

(2020) Stepana Boukalova et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Preparation of human dihydroorotate dehydrogenase for interaction studies with lipid bilayers

(2020) Juan Manuel Orozco Rodriguez et al.   NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS

Five Constituents in Psoralea corylifolia L. Attenuate Palmitic Acid-Induced Hepatocyte Injury via Inhibiting the Protein Kinase C-α/Nicotinamide-Adenine Dinucleotide Phosphate Oxidase Pathway

(2020) Lishan Zhou et al.   Frontiers in Pharmacology

A non-proliferative role of pyrimidine metabolism in cancer

(2020) Aarif Siddiqui et al.   Molecular Metabolism

Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability

(2020) Gergana Popova et al.   JOURNAL OF MEDICINAL CHEMISTRY

Repositioning an Immunomodulatory Drug Vidofludimus as a Farnesoid X Receptor Modulator With Therapeutic Effects on NAFLD

(2020) Yanlin Zhu et al.   Frontiers in Pharmacology

Natural product piperine alleviates experimental allergic encephalomyelitis in mice by targeting dihydroorotate dehydrogenase

(2020) Zehui Liu et al.   BIOCHEMICAL PHARMACOLOGY

Mitochondrial ubiquinol oxidation is necessary for tumour growth

(2020) Inmaculada Martínez-Reyes et al.   NATURE

Leflunomide triggers synthetic lethality in PTEN-deficient prostate cancer

(2020) Sait Ozturk et al.   PROSTATE CANCER AND PROSTATIC DISEASES

Vidofludimus calcium, a next generation DHODH inhibitor for the Treatment of relapsing-remitting multiple sclerosis

(2020) Andreas Muehler et al.   Multiple Sclerosis and Related Disorders

Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase

(2020) Gabrielle McDonald et al.   MOLECULAR CANCER THERAPEUTICS

Elevated DHODH expression promotes cell proliferation via stabilizing β-catenin in esophageal squamous cell carcinoma

(2020) Yu Qian et al.   Cell Death & Disease

Potent human dihydroorotate dehydrogenase inhibitory activity of new quinoline-4-carboxylic acids derived from phenolic aldehydes: Synthesis, cytotoxicity, lipophilicity and molecular docking studies

(2020) Milena M. Petrović et al.   BIOORGANIC CHEMISTRY

A comprehensive drug repurposing study for COVID19 treatment: novel putative dihydroorotate dehydrogenase inhibitors show association to serotonin–dopamine receptors

(2020) Burak Berber et al.   BRIEFINGS IN BIOINFORMATICS

Leflunomide Suppresses the Growth of LKB1-Inactivated Tumors in the Immune-Competent Host and Attenuates Distant Cancer Metastasis

(2020) Rui Jin et al.   MOLECULAR CANCER THERAPEUTICS

Inhibition of the de novo pyrimidine biosynthesis pathway limits ribosomal RNA transcription causing nucleolar stress in glioblastoma cells

(2020) M. Carmen Lafita-Navarro et al.   PLoS Genetics

Re-evaluation of Brequinar sodium, a dihydroorotate dehydrogenase inhibitor

(2019) Godefridus J. Peters   NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS

Characteristics, Biological Properties and Analytical Methods of Piperine: A Review

(2019) Christian Rafael Quijia et al.   CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY

Synthesis of 2-,4,-6-, and/or 7-substituted quinoline derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents: 3D QSAR-assisted design

(2019) Vivek K. Vyas et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Reversible alopecia areata: a little known side effect of leflunomide

(2019) Greg Koller et al.   CLINICAL RHEUMATOLOGY

The novel dihydroorotate dehydrogenase (DHODH) inhibitor BAY 2402234 triggers differentiation and is effective in the treatment of myeloid malignancies

(2019) Sven Christian et al.   LEUKEMIA

Isobavachalcone isolated from Psoralea corylifolia inhibits cell proliferation and induces apoptosis via inhibiting the AKT/GSK-3β/β-catenin pathway in colorectal cancer cells

(2019) Yanxi Li et al.   Drug Design Development and Therapy

Leflunomide Synergizes with Gemcitabine in Growth Inhibition of Pancreatic Cancer Cells and Impairs c-Myc Signaling through PIM Kinase Targeting

(2019) Ralf Buettner et al.   Molecular Therapy-Oncolytics

Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides

(2019) Elodie Villa et al.   Cancers

Structural Optimization and Structure–Activity Relationship of 4-Thiazolidinone Derivatives as Novel Inhibitors of Human Dihydroorotate Dehydrogenase

(2019) Fanxun Zeng et al.   MOLECULES

Mechanisms explaining the efficacy of psoralidin in cancer and osteoporosis, a review

(2019) Zhenlong Xin et al.   PHARMACOLOGICAL RESEARCH

Targeting pyrimidine synthesis accentuates molecular therapy response in glioblastoma stem cells

(2019) Xiuxing Wang et al.   Science Translational Medicine

UVB-induced DHODH upregulation, which is driven by STAT3, is a promising target for chemoprevention and combination therapy of photocarcinogenesis

(2019) Mohsen Hosseini et al.   Oncogenesis

Inhibition of De Novo Pyrimidine Nucleotide Synthesis By the Novel DHODH Inhibitor PTC299 Induces Differentiation and/or Death of AML Cells

(2019) Marla Weetall et al.   BLOOD

Targeting DHODH with AG-636 Induces Apoptosis and Differentiation and Inhibits Mitochondrial Function in AML, Translating into Anti-Tumor Efficacy in Vitro and in Vivo

(2019) Zhihong Zeng et al.   BLOOD

Hematologic Malignancies Exhibit Selective Vulnerability to Inhibition of De Novo Pyrimidine Biosynthesis By AG-636, a Novel Inhibitor of Dihydroorotate Dehydrogenase in Phase 1 Clinical Trials

(2019) Danielle Ulanet et al.   BLOOD

ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia

(2019) Jianbiao Zhou et al.   HAEMATOLOGICA

Identification of DHODH as a therapeutic target in small cell lung cancer

(2019) Leanne Li et al.   Science Translational Medicine

The chromosome-scale reference genome of black pepper provides insight into piperine biosynthesis

(2019) Lisong Hu et al.   Nature Communications

Identification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma

(2019) Helen Winter et al.   Cancers

Dihydroorotate dehydrogenase inhibitors in anti-infective drug research

(2019) Donatella Boschi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

PCK1 and DHODH drive colorectal cancer liver metastatic colonization and hypoxic growth by promoting nucleotide synthesis

(2019) Norihiro Yamaguchi et al.   eLife

Leflunomide: A promising drug with good antitumor potential

(2018) Chunying Zhang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Targeting Myeloid Differentiation Using Potent 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold-Based Human Dihydroorotate Dehydrogenase Inhibitors

(2018) Stefano Sainas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Biological Evaluation of 4-Quinoline Carboxylic Acids as Inhibitors of Dihydroorotate Dehydrogenase

(2018) Joseph T. Madak et al.   JOURNAL OF MEDICINAL CHEMISTRY

Anti-inflammatory drug, leflunomide and its metabolite teriflunomide inhibit NSCLC proliferation in vivo and in vitro

(2018) Liyang Jiang et al.   TOXICOLOGY LETTERS

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

(2018) Marcus J. G. W. Ladds et al.   Nature Communications

Differential Effector Engagement by Oncogenic KRAS

(2018) Tina L. Yuan et al.   Cell Reports

Crystal structures of FMN-bound and FMN-free forms of dihydroorotate dehydrogenase from Trypanosoma brucei

(2018) Tomomi Kubota et al.   FEBS Open Bio

Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells

(2018) Martina Bajzikova et al.   Cell Metabolism

The emergence of dihydroorotate dehydrogenase (DHODH) as a therapeutic target in acute myeloid leukemia

(2018) David B. Sykes   EXPERT OPINION ON THERAPEUTIC TARGETS

Targeting of Hematologic Malignancies with PTC299, A Novel Potent Inhibitor of Dihydroorotate Dehydrogenase with Favorable Pharmaceutical Properties

(2018) Liangxian Cao et al.   MOLECULAR CANCER THERAPEUTICS

Revisiting the role of dihydroorotate dehydrogenase as a therapeutic target for cancer

(2018) Joseph T. Madak et al.   PHARMACOLOGY & THERAPEUTICS

Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin

(2018) Mathura Subangari Dorasamy et al.   BIOMEDICINE & PHARMACOTHERAPY

Design, synthesis, biological evaluation and X-ray structural studies of potent human dihydroorotate dehydrogenase inhibitors based on hydroxylated azole scaffolds

(2017) Stefano Sainas et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell carcinoma

(2017) Aishu Ren et al.   Molecular Medicine Reports

Synthesis, structure–activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase

(2017) Fanxun Zeng et al.   MedChemComm

Isobavachalcone inhibits the proliferation and invasion of tongue squamous cell carcinoma cells

(2017) Yi Shi et al.   Oncology Letters

PTEN Regulates Glutamine Flux to Pyrimidine Synthesis and Sensitivity to Dihydroorotate Dehydrogenase Inhibition

(2017) Deepti Mathur et al.   Cancer Discovery

Adaptive Reprogramming of De Novo Pyrimidine Synthesis Is a Metabolic Vulnerability in Triple-Negative Breast Cancer

(2017) Kristin K. Brown et al.   Cancer Discovery

Dihydroorotate dehydrogenase Inhibitors Target c-Myc and Arrest Melanoma, Myeloma and Lymphoma cells at S-phase

(2017) Mathura Subangari Dorasamy et al.   Journal of Cancer

Design, synthesis, crystal structure and in vitro cytotoxic properties of a novel Schiff base derived from indole and biphenyl

(2017) Fan-Zhi Bu et al.   Acta Crystallographica Section C-Structural Chemistry

Inhibition of Dihydroorotate Dehydrogenase Overcomes Differentiation Blockade in Acute Myeloid Leukemia

(2016) David B. Sykes et al.   CELL

Development of ML390: A Human DHODH Inhibitor That Induces Differentiation in Acute Myeloid Leukemia

(2016) Timothy A. Lewis et al.   ACS Medicinal Chemistry Letters

Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH

(2015) Iskandar Abdullah et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Pyrimidine Metabolism: Dynamic and Versatile Pathways in Pathogens and Cellular Development

(2015) Manuel F. Garavito et al.   Journal of Genetics and Genomics

Design, Synthesis, X-ray Crystallographic Analysis, and Biological Evaluation of Thiazole Derivatives as Potent and Selective Inhibitors of Human Dihydroorotate Dehydrogenase

(2015) Junsheng Zhu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Isobavachalcone induces the apoptosis of gastric cancer cells via inhibition of the Akt and Erk pathways

(2015) XIAOHONG JIN et al.   Experimental and Therapeutic Medicine

Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases

(2015) Yara Dadalti Fragoso et al.   Expert Review of Clinical Pharmacology

Comparison of Two Molecular Scaffolds, 5-Methylisoxazole-3-Carboxamide and 5-Methylisoxazole-4-Carboxamide

(2014) Yaoming Song et al.   CURRENT PHARMACEUTICAL DESIGN

Design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents

(2014) Vivek K. Vyas et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Mitochondrial Respiratory Supercomplex Association Limits Production of Reactive Oxygen Species from Complex I

(2013) Evelina Maranzana et al.   ANTIOXIDANTS & REDOX SIGNALING

On Dihydroorotate Dehydrogenases and Their Inhibitors and Uses

(2013) Hélène Munier-Lehmann et al.   JOURNAL OF MEDICINAL CHEMISTRY

The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro

(2013) Li Li et al.   JOURNAL OF NEUROIMMUNOLOGY

Pyrimidine homeostasis is accomplished by directed overflow metabolism

(2013) Marshall Louis Reaves et al.   NATURE

Lapachol and its congeners as anticancer agents: a review

(2013) Francesco Epifano et al.   PHYTOCHEMISTRY REVIEWS

Teriflunomide in relapsing multiple sclerosis: therapeutic utility

(2013) Mark S. Freedman   Therapeutic Advances in Chronic Disease

Profiling of dihydroorotate dehydrogenase, p38 and JAK inhibitors in the rat adjuvant-induced arthritis model: a translational study

(2012) C Balagué et al.   BRITISH JOURNAL OF PHARMACOLOGY

Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism

(2012) Haoqiang Ying et al.   CELL

Discovery of Diverse Human Dihydroorotate Dehydrogenase Inhibitors as Immunosuppressive Agents by Structure-Based Virtual Screening

(2012) Yanyan Diao et al.   JOURNAL OF MEDICINAL CHEMISTRY

The role of fluorine in stabilizing the bioactive conformation of dihydroorotate dehydrogenase inhibitors

(2012) Silvia Bonomo et al.   JOURNAL OF MOLECULAR MODELING

Evidence supporting a role for dihydroorotate dehydrogenase, bioenergetics, and p53 in selective teriflunomide-induced apoptosis in transformed versus normal human keratinocytes

(2011) Numsen Hail et al.   APOPTOSIS

Recent Developments in the Medicinal Chemistry and Therapeutic Potential of Dihydroorotate Dehydrogenase (DHODH) Inhibitors

(2011) V. K. Vyas et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

DHODH modulates transcriptional elongation in the neural crest and melanoma

(2011) Richard Mark White et al.   NATURE

Leflunomide with low-dose everolimus for treatment of Kaposi's sarcoma in a renal allograft recipient

(2011) G. Basu et al.   NEPHROLOGY DIALYSIS TRANSPLANTATION

4SC-101, A Novel Small Molecule Dihydroorotate Dehydrogenase Inhibitor, Suppresses Systemic Lupus Erythematosus in MRL-(Fas)lpr Mice

(2010) Onkar P. Kulkarni et al.   AMERICAN JOURNAL OF PATHOLOGY

Abrogation of Akt signaling by Isobavachalcone contributes to its anti-proliferative effects towards human cancer cells

(2010) Hui Jing et al.   CANCER LETTERS

The mitochondrial respiratory chain

(2010) Peter R. Rich et al.   Essays in Biochemistry

The Anti-Inflammatory Drug Leflunomide Is an Agonist of the Aryl Hydrocarbon Receptor

(2010) Edmond F. O'Donnell et al.   PLoS One

Exome sequencing identifies the cause of a mendelian disorder

(2009) Sarah B Ng et al.   NATURE GENETICS

Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

(2008) Yen-Chun Liu et al.   PLoS One