Selective small-molecule EPAC activators

Inhibition of EPAC2 Attenuates Intracerebral Hemorrhage-Induced Secondary Brain Injury via the p38/BIM/Caspase-3 Pathway

(2019) Yan Zhuang et al.   JOURNAL OF MOLECULAR NEUROSCIENCE

PDE4 and Epac1 Synergistically Promote Rectal Carcinoma via the cAMP Pathway

(2019) Xiangyu Kong et al.   Analytical Cellular Pathology

Phosphodiesterases as therapeutic targets for respiratory diseases

(2019) Haoxiao Zuo et al.   PHARMACOLOGY & THERAPEUTICS

Function of cAMP scaffolds in obstructive lung disease: Focus on epithelial‐to‐mesenchymal transition and oxidative stress

(2019) Haoxiao Zuo et al.   BRITISH JOURNAL OF PHARMACOLOGY

Fusion pore regulation by cAMP/Epac2 controls cargo release during insulin exocytosis

(2019) Alenka Guček et al.   eLife

β Cell–intrinsic β-arrestin 1 signaling enhances sulfonylurea-induced insulin secretion

(2019) Luiz F. Barella et al.   JOURNAL OF CLINICAL INVESTIGATION

Elevated cyclic-AMP represses expression of exchange protein activated by cAMP (EPAC1) by inhibiting YAP-TEAD activity and HDAC-mediated histone deacetylation

(2019) Reza Ebrahimighaei et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

The IL-6/STAT3 pathway regulates adhesion molecules and cytoskeleton of endothelial cells in thromboangiitis obliterans

(2018) Zheng Wei et al.   CELLULAR SIGNALLING

Adenylate cyclases: Receivers, transducers, and generators of signals

(2018) Jens Bassler et al.   CELLULAR SIGNALLING

Anti-inflammatory effects of the phosphodiesterase type 4 inhibitor CHF6001 on bronchoalveolar lavage lymphocytes from asthma patients

(2018) Thomas Southworth et al.   CYTOKINE

Inhibitors of phosphodiesterase as cancer therapeutics

(2018) Ting Peng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy

(2018) et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Inflammation Induces Epac Protein Kinase Alpha and Epsilon Signaling in TRPV1-Mediated Hyperalgesia

(2018) Yanping Gu et al.   PAIN

Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development

(2018) William G. Robichaux et al.   PHYSIOLOGICAL REVIEWS

cAMP: From Long-Range Second Messenger to Nanodomain Signalling

(2018) Nshunge Musheshe et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Dynamic expression of Epac and Rap1 in mouse oocytes and preimplantation embryos

(2018) Jun‑Chao Wang et al.   Experimental and Therapeutic Medicine

Inhibition of Epac2 Attenuates Neural Cell Apoptosis and Improves Neurological Deficits in a Rat Model of Traumatic Brain Injury

(2018) Ling Zhang et al.   Frontiers in Neuroscience

Usefulness of Exchanged Protein Directly Activated by cAMP (Epac)1-Inhibiting Therapy for Prevention of Atrial and Ventricular Arrhythmias in Mice

(2018) Rajesh Prajapati et al.   CIRCULATION JOURNAL

cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits

(2018) Sendi Rafael Adame-García et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells

(2018) Aleksandra Drelich et al.   Viruses-Basel

The novel exchange protein activated by cyclic AMP 1 (EPAC1) agonist, I942, regulates inflammatory gene expression in human umbilical vascular endothelial cells (HUVECs)

(2018) Jolanta Wiejak et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue

(2017) Marco Spadaccini et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

EPAC1 overexpression is a prognostic marker and its inhibition shows promising therapeutic potential for gastric cancer

(2017) Ding-Ping Sun et al.   ONCOLOGY REPORTS

A facile synthesis of sulfonylureas via water assisted preparation of carbamates

(2017) Dinesh Kumar Tanwar et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases

(2017) Carmen W. Dessauer et al.   PHARMACOLOGICAL REVIEWS

Adenylyl cyclase signalling complexes – Pharmacological challenges and opportunities

(2017) Michelle L. Halls et al.   PHARMACOLOGY & THERAPEUTICS

Phenotypic, chemical and functional characterization of cyclic nucleotide phosphodiesterase 4 (PDE4) as a potential anthelmintic drug target

(2017) Thavy Long et al.   PLoS Neglected Tropical Diseases

Comparison of Three-Dimensional Ligand-based Pharmacophores among 11 Phosphodiesterases (PDE 1 to PDE 11) Pharmacophores

(2017) Sei-Hwan Kim et al.   BULLETIN OF THE KOREAN CHEMICAL SOCIETY

Activation of G protein-coupled estrogen receptor 1 induces coronary artery relaxation via Epac/Rap1-mediated inhibition of RhoA/Rho kinase pathway in parallel with PKA

(2017) Xuan Yu et al.   PLoS One

The phosphodiesterase inhibitor, ibudilast, attenuates neuroinflammation in the MPTP model of Parkinson’s disease

(2017) Joanna Schwenkgrub et al.   PLoS One

Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1

(2017) Euan Parnell et al.   Scientific Reports

Protein–protein interactions of PDE4 family members — Functions, interactions and therapeutic value

(2016) Enno Klussmann   CELLULAR SIGNALLING

White Adipocyte Adiponectin Exocytosis Is Stimulated via β 3 -Adrenergic Signaling and Activation of Epac1: Catecholamine Resistance in Obesity and Type 2 Diabetes

(2016) Ali M. Komai et al.   DIABETES

Sulphonylurea receptor-1, sulphonylureas and amplification of insulin secretion by Epac activation in β cells

(2016) M. Nenquin et al.   DIABETES OBESITY & METABOLISM

POPDC proteins as potential novel therapeutic targets in cancer

(2016) Johanna N. Amunjela et al.   DRUG DISCOVERY TODAY

Structure and functional roles of Epac2 (Rapgef4)

(2016) Kenji Sugawara et al.   GENE

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance

(2016) M Hwang et al.   INTERNATIONAL JOURNAL OF OBESITY

Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1

(2016) Pooja Singhmar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Popeye domain containing protein family – A novel class of cAMP effectors with important functions in multiple tissues

(2016) Roland F.R. Schindler et al.   PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY

Signal transduction in the hypothalamic corticotropin-releasing factor system and its clinical implications

(2016) Kazunori Kageyama et al.   STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS

Pharmacological targeting of AKAP-directed compartmentalized cAMP signalling

(2015) Alessandro Dema et al.   CELLULAR SIGNALLING

Exchange protein directly activated by cAMP encoded by the mammalian rapgef3 gene: Structure, function and therapeutics

(2015) Upasana Banerjee et al.   GENE

Structure-Guided Design of Selective Epac1 and Epac2 Agonists

(2015) Frank Schwede et al.   PLOS BIOLOGY

Targeting protein–protein interactions in complexes organized by A kinase anchoring proteins

(2015) Ana I. Calejo et al.   Frontiers in Pharmacology

Biochemical and Pharmacological Characterizations of ESI-09 Based EPAC Inhibitors: Defining the ESI-09 “Therapeutic Window”

(2015) Yingmin Zhu et al.   Scientific Reports

Rap1b in Smooth Muscle and Endothelium Is Required for Maintenance of Vascular Tone and Normal Blood Pressure

(2014) S. Lakshmikanthan et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Cyclic nucleotide phosphodiesterases (PDEs): coincidence detectors acting to spatially and temporally integrate cyclic nucleotide and non-cyclic nucleotide signals: Figure 1

(2014) Donald H. Maurice et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Exchange protein directly activated by cAMP 1 promotes autophagy during cardiomyocyte hypertrophy

(2014) Anne-Coline Laurent et al.   CARDIOVASCULAR RESEARCH

Routes to cAMP: shaping neuronal connectivity with distinct adenylate cyclases

(2014) Xavier Nicol et al.   EUROPEAN JOURNAL OF NEUROSCIENCE

Epac1 and Epac2 are differentially involved in inflammatory and remodeling processes induced by cigarette smoke

(2014) Anouk Oldenburger et al.   FASEB JOURNAL

Allosteric Inhibition of Epac

(2014) Loren M. Brown et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Epac-Rap Signaling Reduces Oxidative Stress in the Tubular Epithelium

(2014) G. Stokman et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Advances in targeting cyclic nucleotide phosphodiesterases

(2014) Donald H. Maurice et al.   NATURE REVIEWS DRUG DISCOVERY

Cyclic Nucleotide Phosphodiesterases: important signaling modulators and therapeutic targets

(2014) F Ahmad et al.   ORAL DISEASES

Introduction of Aromatic Ring-Containing Substituents in Cyclic Nucleotides Is Associated with Inhibition of Toxin Uptake by the Hepatocyte Transporters OATP 1B1 and 1B3

(2014) Lars Herfindal et al.   PLoS One

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

(2013) Diego Carnaroglio et al.   Beilstein Journal of Organic Chemistry

Off-target effect of the Epac agonist 8-pCPT-2′-O-Me-cAMP on P2Y12 receptors in blood platelets

(2013) Lars Herfindal et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Carboxylic Acid (Bio)Isosteres in Drug Design

(2013) Carlo Ballatore et al.   ChemMedChem

Epac2 Mediates Cardiac β1-Adrenergic–Dependent Sarcoplasmic Reticulum Ca 2+ Leak and Arrhythmia

(2013) Laëtitia Pereira et al.   CIRCULATION

Sustainable routes to polyurethane precursors

(2013) Oliver Kreye et al.   GREEN CHEMISTRY

New perspectives in cyclic nucleotide-mediated functions in the CNS: the emerging role of cyclic nucleotide-gated (CNG) channels

(2013) Maria Vittoria Podda et al.   PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

DNA Methylation of Alternative Promoters Directs Tissue Specific Expression of Epac2 Isoforms

(2013) Erling A. Hoivik et al.   PLoS One

Identification of a Tetrahydroquinoline Analog as a Pharmacological Inhibitor of the cAMP-binding Protein Epac

(2012) Delphine Courilleau et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Distinct PKA and Epac compartmentalization in airway function and plasticity

(2012) Bart G.J. Dekkers et al.   PHARMACOLOGY & THERAPEUTICS

Protein kinase A and the exchange protein directly activated by cAMP (Epac) modulate phenotype plasticity in human airway smooth muscle

(2011) Sara S Roscioni et al.   BRITISH JOURNAL OF PHARMACOLOGY

Direct Activation of Epac by Sulfonylurea Is Isoform Selective

(2011) Katie J. Herbst et al.   CHEMISTRY & BIOLOGY

Synopsis of Some Recent Tactical Application of Bioisosteres in Drug Design

(2011) Nicholas A. Meanwell   JOURNAL OF MEDICINAL CHEMISTRY

Epac-Rap Signaling Reduces Cellular Stress and Ischemia-induced Kidney Failure

(2011) G. Stokman et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Exchange Protein Directly Activated by Cyclic AMP Isoform 2 Is Not a Direct Target of Sulfonylurea Drugs

(2010) Tamara Tsalkova et al.   ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES

8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties

(2010) Maria Grandoch et al.   THROMBOSIS AND HAEMOSTASIS

Facilitation of β-cell KATPchannel sulfonylurea sensitivity by a cAMP analog selective for the cAMP-regulated guanine nucleotide exchange factor Epac

(2010) Colin A. Leech et al.   Islets

Mechanism of Epac Activation

(2009) Tamara Tsalkova et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

In Vitro Skin Diffusion Study of Pure Forskolin versus a Forskolin-ContainingPlectranthus barbatusRoot Extract

(2009) Jing Chen et al.   JOURNAL OF NATURAL PRODUCTS

Metabolites of an Epac-Selective cAMP Analog Induce Cortisol Synthesis by Adrenocortical Cells through a cAMP-Independent Pathway

(2009) Judith A. Enyeart et al.   PLoS One

The cAMP Sensor Epac2 Is a Direct Target of Antidiabetic Sulfonylurea Drugs

(2009) C.-L. Zhang et al.   SCIENCE

Epac and PKA: a tale of two intracellular cAMP receptors

(2008) Xiaodong Cheng et al.   ACTA BIOCHIMICA ET BIOPHYSICA SINICA

8-pCPT-2′-O-Me-cAMP-AM: An Improved Epac-Selective cAMP Analogue

(2008) Marjolein J. Vliem et al.   CHEMBIOCHEM

Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B

(2008) Holger Rehmann et al.   NATURE

Cyclic nucleotide analogs as probes of signaling pathways

(2008) Heiko Poppe et al.   NATURE METHODS

Epac activation, altered calcium homeostasis and ventricular arrhythmogenesis in the murine heart

(2008) Sandeep S. Hothi et al.   PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY