Small-molecule modulators of the circadian clock: Pharmacological potentials in circadian-related diseases

A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude

(2020) Yagmur Umay Doruk et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Isoform-selective regulation of mammalian cryptochromes

(2020) Simon Miller et al.   Nature Chemical Biology

Chemical perturbations reveal that RUVBL2 regulates the circadian phase in mammals

(2020) Dapeng Ju et al.   Science Translational Medicine

Sex‐dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial

(2020) Pasquale F. Innominato et al.   Cancer Medicine

The Core-Clock Gene NR1D1 Impacts Cell Motility In Vitro and Invasiveness in a Zebrafish Xenograft Colon Cancer Model

(2020) Alireza Basti et al.   Cancers

Nobiletin affects circadian rhythms and oncogenic characteristics in a cell-dependent manner

(2020) Sujeewa S. Lellupitiyage Don et al.   PLoS One

An Optimal Time for Treatment—Predicting Circadian Time by Machine Learning and Mathematical Modelling

(2020) Janina Hesse et al.   Cancers

Properties of FDA-approved small molecule protein kinase inhibitors

(2019) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Phase 1 Open-Label, Multicenter Study of First-in-Class RORγ Agonist LYC-55716: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity

(2019) Devalingam Mahalingam et al.   CLINICAL CANCER RESEARCH

Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORγ inverse agonists

(2019) Jérôme Amaudrut et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The importance of determining circadian parameters in pharmacological studies

(2019) Laetitia Gaspar et al.   BRITISH JOURNAL OF PHARMACOLOGY

Discovery of potent and orally bioavailable inverse agonists of the retinoic acid receptor-related orphan receptor C2

(2019) Stefan von Berg et al.   ACS Medicinal Chemistry Letters

The Role of 17β-Estradiol and Estrogen Receptors in Regulation of Ca2+ Channels and Mitochondrial Function in Cardiomyocytes

(2019) Shokoufeh Mahmoodzadeh et al.   Frontiers in Endocrinology

Medicine in the Fourth Dimension

(2019) Christopher R. Cederroth et al.   Cell Metabolism

Nobiletin fortifies mitochondrial respiration in skeletal muscle to promote healthy aging against metabolic challenge

(2019) Kazunari Nohara et al.   Nature Communications

Development and Therapeutic Potential of Small-Molecule Modulators of Circadian Systems

(2018) Zheng Chen et al.   Annual Review of Pharmacology and Toxicology

Identification of circadian clock modulators from existing drugs

(2018) T Katherine Tamai et al.   EMBO Molecular Medicine

Combating Autoimmune Diseases With Retinoic Acid Receptor-Related Orphan Receptor-γ (RORγ or RORc) Inhibitors: Hits and Misses

(2018) Vrajesh Bhaskarbhai Pandya et al.   JOURNAL OF MEDICINAL CHEMISTRY

The cryptochrome inhibitor KS15 enhances E-box-mediated transcription by disrupting the feedback action of a circadian transcription-repressor complex

(2018) Jaebong Jang et al.   LIFE SCIENCES

CLOCKΔ19 mutation modifies the manner of synchrony among oscillation neurons in the suprachiasmatic nucleus

(2018) Mitsugu Sujino et al.   Scientific Reports

Transcription Factor Retinoid-Related Orphan Receptor γt: A Promising Target for the Treatment of Psoriasis

(2018) Lipeng Tang et al.   Frontiers in Immunology

Altered Circadian Rhythms and Breast Cancer: From the Human to the Molecular Level

(2018) Hui-Hsien Lin et al.   Frontiers in Endocrinology

The Opportunities and Challenges of Peroxisome Proliferator-Activated Receptors Ligands in Clinical Drug Discovery and Development

(2018) Fan Hong et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Discovery of 3-Cyano-N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist

(2018) Mark E. Schnute et al.   JOURNAL OF MEDICINAL CHEMISTRY

Medicine’s secret ingredient — it’s in the timing

(2018) Lynne Peeples   NATURE

Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence

(2018) Gabriele Sulli et al.   NATURE

The emerging link between cancer, metabolism, and circadian rhythms

(2018) Selma Masri et al.   NATURE MEDICINE

Computational and experimental insights into the circadian effects of SIRT1

(2018) Panagiota T. Foteinou et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

What’s next for chronobiology and drug discovery

(2017) Zheng Chen   Expert Opinion on Drug Discovery

Evolution of circadian rhythms: from bacteria to human

(2017) Utpal Bhadra et al.   SLEEP MEDICINE

Clock-Enhancing Small Molecules and Potential Applications in Chronic Diseases and Aging

(2017) Gabrielle F. Gloston et al.   Frontiers in Neurology

Potent Effects of Flavonoid Nobiletin on Amplitude, Period, and Phase of the Circadian Clock Rhythm in PER2::LUCIFERASE Mouse Embryonic Fibroblasts

(2017) Ayako Shinozaki et al.   PLoS One

Recent progress on nuclear receptor RORγ modulators

(2016) Patrick Cyr et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Small Molecule Nobiletin Targets the Molecular Oscillator to Enhance Circadian Rhythms and Protect against Metabolic Syndrome

(2016) Baokun He et al.   Cell Metabolism

Molecular Targets for Small-Molecule Modulators of Circadian Clocks

(2016) Baokun He et al.   CURRENT DRUG METABOLISM

Circadian clocks govern calorie restriction–mediated life span extension through BMAL1- and IGF-1-dependent mechanisms

(2016) Sonal A. Patel et al.   FASEB JOURNAL

Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects

(2016) S. Brunner-Ziegler et al.   JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells

(2016) David R Withers et al.   NATURE MEDICINE

ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer

(2016) Junjian Wang et al.   NATURE MEDICINE

Transcriptional architecture of the mammalian circadian clock

(2016) Joseph S. Takahashi   NATURE REVIEWS GENETICS

Immunity around the clock

(2016) Kevin Man et al.   SCIENCE

Circadian time signatures of fitness and disease

(2016) Joseph Bass et al.   SCIENCE

Dosing-Time Makes the Poison: Circadian Regulation and Pharmacotherapy

(2016) Robert Dallmann et al.   TRENDS IN MOLECULAR MEDICINE

Therapeutic Effect of a Synthetic RORα/γ Agonist in an Animal Model of Autism

(2015) Yongjun Wang et al.   ACS Chemical Neuroscience

CH Activation Generates Period-Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock

(2015) Tsuyoshi Oshima et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

(2015) Sung Kook Chun et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Resveratrol restores the circadian rhythmic disorder of lipid metabolism induced by high-fat diet in mice

(2015) Linjie Sun et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Development of Small-Molecule Cryptochrome Stabilizer Derivatives as Modulators of the Circadian Clock

(2015) Jae Wook Lee et al.   ChemMedChem

Chemical chronobiology: Toward drugs manipulating time

(2015) Thomas Wallach et al.   FEBS LETTERS

Retinoic acid-related orphan receptor alpha reprograms glucose metabolism in glutamine-deficient hepatoma cells

(2015) Jun-Kyu Byun et al.   HEPATOLOGY

Digoxin ameliorates autoimmune arthritis via suppression of Th17 differentiation

(2015) Jennifer Lee et al.   INTERNATIONAL IMMUNOPHARMACOLOGY

Selenium is a modulator of circadian clock that protects mice from the toxicity of a chemotherapeutic drug via upregulation of the core clock protein, BMAL1

(2015) Yan Hu et al.   Oncotarget

Identification and Validation of Cryptochrome Inhibitors That Modulate the Molecular Circadian Clock

(2014) Sung Kook Chun et al.   ACS Chemical Biology

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

(2014) Daisuke Kondoh et al.   BIOLOGICAL & PHARMACEUTICAL BULLETIN

Impact of Circadian Nuclear Receptor REV-ERBα on Midbrain Dopamine Production and Mood Regulation

(2014) Sooyoung Chung et al.   CELL

Small-Molecule RORγt Antagonists Inhibit T Helper 17 Cell Transcriptional Network by Divergent Mechanisms

(2014) Sheng Xiao et al.   IMMUNITY

Pharmacologic Inhibition of ROR t Regulates Th17 Signature Gene Expression and Suppresses Cutaneous Inflammation In Vivo

(2014) J. Skepner et al.   JOURNAL OF IMMUNOLOGY

REV-ERB and ROR nuclear receptors as drug targets

(2014) Douglas J. Kojetin et al.   NATURE REVIEWS DRUG DISCOVERY

Dual inhibition of REV-ERBβ and autophagy as a novel pharmacological approach to induce cytotoxicity in cancer cells

(2014) C De Mei et al.   ONCOGENE

A circadian gene expression atlas in mammals: Implications for biology and medicine

(2014) Ray Zhang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Small molecule SIRT1 activators for the treatment of aging and age-related diseases

(2014) Basil P. Hubbard et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour

(2014) Subhashis Banerjee et al.   Nature Communications

Structures of Drosophila Cryptochrome and Mouse Cryptochrome1 Provide Insight into Circadian Function

(2013) Anna Czarna et al.   CELL

Optimized Chemical Probes for REV-ERBα

(2013) Ryan P. Trump et al.   JOURNAL OF MEDICINAL CHEMISTRY

Rev-erb-α modulates skeletal muscle oxidative capacity by regulating mitochondrial biogenesis and autophagy

(2013) Estelle Woldt et al.   NATURE MEDICINE

Involvement of the Clock Gene Rev-erb alpha in the Regulation of Glucagon Secretion in Pancreatic Alpha-Cells

(2013) Elaine Vieira et al.   PLoS One

Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1

(2013) Marina M. Bellet et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag

(2013) Yoshiaki Yamaguchi et al.   SCIENCE

Aging signaling pathways and circadian clock-dependent metabolic derangements

(2013) Maria Florencia Tevy et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

How to fix a broken clock

(2013) Analyne M. Schroeder et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Pharmacologic Repression of Retinoic Acid Receptor-Related Orphan Nuclear Receptor γ Is Therapeutic in the Collagen-Induced Arthritis Experimental Model

(2013) Mi Ra Chang et al.   Arthritis & Rheumatology

Identification of a Selective RORγ Ligand That Suppresses TH17 Cells and Stimulates T Regulatory Cells

(2012) Laura A. Solt et al.   ACS Chemical Biology

Identification of SR2211: A Potent Synthetic RORγ-Selective Modulator

(2012) Naresh Kumar et al.   ACS Chemical Biology

Metformin affects the circadian clock and metabolic rhythms in a tissue-specific manner

(2012) Maayan Barnea et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet

(2012) Megumi Hatori et al.   Cell Metabolism

Small molecule modifiers of circadian clocks

(2012) Zheng Chen et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Retinoid Receptors and Therapeutic Applications of RAR/RXR Modulators

(2012) Albane le Maire et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists

(2012) Laura A. Solt et al.   NATURE

Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period

(2012) Yoshiaki Onishi et al.   NUCLEIC ACIDS RESEARCH

Identification of Small Molecule Activators of Cryptochrome

(2012) T. Hirota et al.   SCIENCE

Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance

(2011) E. E. Mulvihill et al.   DIABETES

Circadian clocks and drug delivery systems: impact and opportunities in chronotherapeutics

(2011) Francis Lévi et al.   Expert Opinion on Drug Delivery

Kinases and phosphatases in the mammalian circadian clock

(2011) Silke Reischl et al.   FEBS LETTERS

Ursolic Acid Suppresses Interleukin-17 (IL-17) Production by Selectively Antagonizing the Function of RORγt Protein

(2011) Tao Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Post-transcriptional control of circadian rhythms

(2011) S. Kojima et al.   JOURNAL OF CELL SCIENCE

Age-Related Decline in Circadian Output

(2011) T. J. Nakamura et al.   JOURNAL OF NEUROSCIENCE

Cryptochromes mediate rhythmic repression of the glucocorticoid receptor

(2011) Katja A. Lamia et al.   NATURE

Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORγt activity

(2011) Jun R. Huh et al.   NATURE

Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand

(2011) Laura A. Solt et al.   NATURE

Identification of diverse modulators of central and peripheral circadian clocks by high-throughput chemical screening

(2011) Z. Chen et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The nuclear receptor REV-ERB  mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines

(2011) J. E. Gibbs et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GSK4112, a Small Molecule Chemical Probe for the Cell Biology of the Nuclear Heme Receptor Rev-erbα

(2010) Daniel Grant et al.   ACS Chemical Biology

Identification of SR1078, a Synthetic Agonist for the Orphan Nuclear Receptors RORα and RORγ

(2010) Yongjun Wang et al.   ACS Chemical Biology

Identification of SR8278, a Synthetic Antagonist of the Nuclear Heme Receptor REV-ERB

(2010) Douglas Kojetin et al.   ACS Chemical Biology

Identification of SR3335 (ML-176): A Synthetic RORα Selective Inverse Agonist

(2010) Naresh Kumar et al.   ACS Chemical Biology

A second class of nuclear receptors for oxysterols: Regulation of RORα and RORγ activity by 24S-hydroxycholesterol (cerebrosterol)

(2010) Yongjun Wang et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS

The Core Circadian Gene Cryptochrome 2 Influences Breast Cancer Risk, Possibly by Mediating Hormone Signaling

(2010) A. E. Hoffman et al.   Cancer Prevention Research

Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes

(2010) Q.-J. Meng et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Genome-wide RNAi Screen for Modifiers of the Circadian Clock in Human Cells

(2009) Eric E. Zhang et al.   CELL

A large-scale functional RNAi screen reveals a role for CK2 in the mammalian circadian clock

(2009) B. Maier et al.   GENES & DEVELOPMENT

Modulation of Retinoic Acid Receptor-related Orphan Receptor α and γ Activity by 7-Oxygenated Sterol Ligands

(2009) Yongjun Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Benzenesulfoamide T0901317 [N-(2,2,2-Trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide] Is a Novel Retinoic Acid Receptor-Related Orphan Receptor- /  Inverse Agonist

(2009) N. Kumar et al.   MOLECULAR PHARMACOLOGY

CKI / -dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock

(2009) Y. Isojima et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation

(2009) K. A. Lamia et al.   SCIENCE

Estrogen directly modulates circadian rhythms of PER2 expression in the uterus

(2008) Takahiro J. Nakamura et al.   AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM

SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation

(2008) Gad Asher et al.   CELL

Vascular PPARγ Controls Circadian Variation in Blood Pressure and Heart Rate through Bmal1

(2008) Ningning Wang et al.   Cell Metabolism

Live imaging of alteredperiod1expression in the suprachiasmatic nuclei ofVipr2−/−mice1

(2008) Alun T. L. Hughes et al.   JOURNAL OF NEUROCHEMISTRY

Mitogen-Activated Protein Kinase Is a Functional Component of the Autonomous Circadian System in the Suprachiasmatic Nucleus

(2008) M. Akashi et al.   JOURNAL OF NEUROSCIENCE

A chemical biology approach reveals period shortening of the mammalian circadian clock by specific inhibition of GSK-3 

(2008) T. Hirota et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA