Abstract
Epoxyeicosanoids, including the epoxyeicosatrienoic acids, are signaling molecules which appear to help ameliorate the effects of a wide variety of pathological conditions. The enzyme soluble epoxide hydrolase (sEH) metabolizes these molecules by converting them to their corresponding vicinal diols. Inhibition of sEH either by knockout or chemical inhibitors increases epoxyeicosanoid levels in vivo and provides significant organ protection in models of brain, cardiac, and renal injury. sEH also appears to be involved in modulating inflammation, pain pathways, pulmonary function, hypertension, and diabetes. Potent sEH inhibitors have been developed in academic, pharmaceutical, and biotech laboratories and described in the patent and scientific literature. Most of the inhibitor scaffolds employ a urea or amide which functions as an active-site transition state mimic. Arete Therapeutics compound AR9281 successfully completed phase Ia and Ib studies. A phase IIa proof of concept trial for treatment of impaired glucose tolerance has been completed, but the results are not yet reported.
Keywords: AR9281, BTP2, EPHX2, epoxyeicosatrienoic acid, eicosanoids, sEH, soluble epoxide hydrolase, Multiple Pathologic Conditions, Epoxyeicosanoids, ameliorate, vicinal diols, homodimeric bifunctional enzyme, linoleic acid, pyrophosphates, farnesyl, geranyl-geranyl, cytosol,, endothelial-derived hyperpolarizing factor, transient ischemic attack (TIA), MCAO (Middle Cerebral, HAMMOCK LABORATORY PHARMACOPHORE MODEL, secondary pharmacophore, am-ide, ketone, alcohol, carbamate, benzoheterocycle, alkyl spacers, adamantane piperidinyl ureas, piperidinyl ureas, BOEHRINGER INGELHEIM, HOFFMAN LA ROCHE, TAISHO, MERCK
Current Medicinal Chemistry
Title: Soluble Epoxide Hydrolase Inhibitors and their Potential for Treatment of Multiple Pathologic Conditions
Volume: 18 Issue: 4
Author(s): R. H. Ingraham, R. D. Gless and H. Y. Lo
Affiliation:
Keywords: AR9281, BTP2, EPHX2, epoxyeicosatrienoic acid, eicosanoids, sEH, soluble epoxide hydrolase, Multiple Pathologic Conditions, Epoxyeicosanoids, ameliorate, vicinal diols, homodimeric bifunctional enzyme, linoleic acid, pyrophosphates, farnesyl, geranyl-geranyl, cytosol,, endothelial-derived hyperpolarizing factor, transient ischemic attack (TIA), MCAO (Middle Cerebral, HAMMOCK LABORATORY PHARMACOPHORE MODEL, secondary pharmacophore, am-ide, ketone, alcohol, carbamate, benzoheterocycle, alkyl spacers, adamantane piperidinyl ureas, piperidinyl ureas, BOEHRINGER INGELHEIM, HOFFMAN LA ROCHE, TAISHO, MERCK
Abstract: Epoxyeicosanoids, including the epoxyeicosatrienoic acids, are signaling molecules which appear to help ameliorate the effects of a wide variety of pathological conditions. The enzyme soluble epoxide hydrolase (sEH) metabolizes these molecules by converting them to their corresponding vicinal diols. Inhibition of sEH either by knockout or chemical inhibitors increases epoxyeicosanoid levels in vivo and provides significant organ protection in models of brain, cardiac, and renal injury. sEH also appears to be involved in modulating inflammation, pain pathways, pulmonary function, hypertension, and diabetes. Potent sEH inhibitors have been developed in academic, pharmaceutical, and biotech laboratories and described in the patent and scientific literature. Most of the inhibitor scaffolds employ a urea or amide which functions as an active-site transition state mimic. Arete Therapeutics compound AR9281 successfully completed phase Ia and Ib studies. A phase IIa proof of concept trial for treatment of impaired glucose tolerance has been completed, but the results are not yet reported.
Export Options
About this article
Cite this article as:
H. Ingraham R., D. Gless R. and Y. Lo H., Soluble Epoxide Hydrolase Inhibitors and their Potential for Treatment of Multiple Pathologic Conditions, Current Medicinal Chemistry 2011; 18 (4) . https://dx.doi.org/10.2174/092986711794480212
DOI https://dx.doi.org/10.2174/092986711794480212 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Editorial (Thematic Issue: “Amniotic Fluid Embolism: Novel Biomarkers for Future Diagnostic Investigation and Therapy”)
Current Pharmaceutical Biotechnology Insulin-Like Growth Factor-1, a Potential Predicative Biomarker for Postoperative Delirium Among Elderly Patients with Open Abdominal Surgery
Current Pharmaceutical Design Cardiovascular Disease in Systemic Lupus Erythematosus: The Role of Traditional and Lupus Related Risk Factors
Current Cardiology Reviews Gene Modified Cell Transplantation for Vascular Regeneration
Current Gene Therapy Potential Use of Vanadium Compounds in Therapeutics
Current Medicinal Chemistry Postoperative Care of the Transplanted Patient
Current Cardiology Reviews Natural Compounds Used as Therapies Targeting to Amyotrophic Lateral Sclerosis
Current Pharmaceutical Biotechnology The Beneficial Hemodynamic Actions of SGLT-2 Inhibitors beyond the Management of Hyperglycemia
Current Medicinal Chemistry Microparticles as Biomarkers of Vascular Dysfunction in Metabolic Syndrome and its Individual Components
Current Vascular Pharmacology Updates on HCN Channels in the Heart: Function, Dysfunction and Pharmacology
Current Drug Targets Nutritional and Therapeutic Potential of Garlic and Onion (Allium sp.)
Current Nutrition & Food Science Modulation of P2 Receptors on Pancreatic β-cells by Agonists and Antagonists: A Molecular Target for Type 2 Diabetes Treatment
Current Diabetes Reviews Uric acid and Metabolic Syndrome: What is the Relationship?
Current Rheumatology Reviews Biochemical Screening for in utero Drug Exposure
Drug Metabolism Letters Effect of Aglycon and Glycoside Flavonoid-Enriched Extracts Obtained from Buxus sempervirens L. on Glucose and Lipid Metabolism in Diabetic Rats
Cardiovascular & Hematological Agents in Medicinal Chemistry 30 Years Lost in Anesthesia Theory
Cardiovascular & Hematological Agents in Medicinal Chemistry Vitamin D and Metabolic Syndrome: Is There a Link?
Current Pharmaceutical Design In Vitro Data of Current Therapies for SARS-CoV-2
Current Medicinal Chemistry Metabolic and Cardiovascular Complications of Highly Active Antiretroviral Therapy for HIV Infection
Current HIV Research Hypoxia in Pre-Eclampsia: Cause or Effect?
Current Women`s Health Reviews