A5031532167- Eicosanoids and Hypertension Pharmacology
- Alcohol Consumption and Health Effects
- Hormonal Regulation and Hypertension
- Biochemical Acid Research Studies
- Pharmacogenetics and Drug Metabolism
- Inflammatory mediators and NSAID effects
- Fatty Acid Research and Health
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Pharmacology and Obesity Treatment
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Liver Disease Diagnosis and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Long-Term Effects of COVID-19
- Gene expression and cancer classification
- Diet and metabolism studies
- Alcoholism and Thiamine Deficiency
- Advanced Glycation End Products research
- Genetics, Bioinformatics, and Biomedical Research
- COVID-19 Clinical Research Studies
- Peroxisome Proliferator-Activated Receptors
- Lung Cancer Research Studies
- Adrenal Hormones and Disorders
- Artificial Intelligence in Healthcare
Eicosis (United States)
2016-2025
University of California, Davis
2017-2023
UC Davis Comprehensive Cancer Center
2017-2022
This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without addictive potential opioids. EC5026 acts on cytochrome P450 branch arachidonate cascade to stabilize epoxides polyunsaturated fatty acids (EpFA), which are natural mediators reduce pain, resolve inflammation, maintain normal blood pressure. is a slow-tight binding transition-state mimic inhibits soluble epoxide hydrolase (sEH) at picomolar concentrations. The sEH...
Polyunsaturated fatty acids are metabolized into regulatory lipids important for initiating inflammatory responses in the event of disease or injury and signaling resolution inflammation return to homeostasis. The epoxides linoleic acid (leukotoxins) regulate skin barrier function, perivascular alveolar permeability have been associated with poor outcomes burn patients sepsis. It was later reported that blocking metabolism leukotoxins vicinal diols ameliorated deleterious effects...
Significance Oxylipins alter immune cell function and potentially drive pathophysiology in burn sepsis patients. Past recent data reveal a correlation between increased systemic EpOME levels reduced survival human trauma sepsis. This work extends these studies provides evidence that the downstream sEH-derived metabolites, DiHOMEs, are driving worsening outcomes by altering response. Inhibiting DiHOME metabolite formation with sEH inhibitor,...
Abstract Background Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity and unknown. Methods According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into with or without an anhedonia phenotype. Then, protein expression cytokines assessed in selected tissues....
Nanobodies have been progressively replacing traditional antibodies in various immunological methods. However, the use of nanobodies as capture is greatly hampered by their poor performance after passive adsorption to polystyrene microplates, and this restricts full double sandwich enzyme-linked immunosorbent assays (ELISAs). Herein, using human soluble epoxide hydrolase (sEH) a model analyte, we found that both immobilization format blocking agent significant influence on immobilized...
Osteoarthritis (OA) is a degenerative joint disease that causes pain and bone deterioration driven by an increase in prostaglandins (PGs) inflammatory cytokines. Current treatments focus on inhibiting prostaglandin production, pro-inflammatory lipid metabolite, with NSAID drugs; however, other signaling targets could provide safer more effective treatment strategies. Epoxides of polyunsaturated fatty acids (PUFAs) are anti-inflammatory mediators rapidly metabolized the soluble epoxide...
Abstract Chronic pain represents a significant unmet medical need, affecting one‐fifth of the U.S. population. EC5026 is small molecule inhibitor enzyme soluble epoxide hydrolase (sEH) which being developed as novel non‐opioid, non‐NSAID analgesic. prolongs action epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated safety and pharmacokinetic profile in two phase I trials, single‐ascending dose (SAD) study fed‐fasted study. The SAD doses...
COVID-19 serological test must have high sensitivity as well specificity to rule out cross-reactivity with common coronaviruses (HCoVs). We developed a quantitative multiplex test, measuring antibodies against spike (S) proteins of SARS-CoV-2, SARS-CoV, MERS-CoV, and human coronavirus strains (229E, NL63, OC43, HKU1), nucleocapsid (N) protein SARS-CoV viruses. Receptor binding domain S SARS-CoV-2 (S-RBD), N protein, demonstrated (94% 92.5%, respectively) in patients (n = 53), 98%...
<title>Abstract</title> Although high-throughput DNA/RNA sequencing technologies have generated massive genetic and genomic data in human disease, these findings not been translated into new patient treatments. To address this problem, we utilized Mendelian randomization (MR) large patient-level functional to evaluate druggable targets using Alzheimer’s disease (AD) as a prototypical example. Specifically, applied the instruments from 9 expression quantitative trait loci (eQTL) 3 protein...
1-(1-Propionylpiperidin-4-yl)-3-(4-(trifluoromethoxy)phenyl)urea (TPPU) is a potent soluble epoxide hydrolase (sEH) inhibitor that used extensively for modulating inflammation and protecting against hypertension, neuropathic pain neurodegeneration. Despite its wide use in various animal disease models, the metabolism of TPPU has not been well studied. Herein, we describe identification metabolites using LC-MS/MS strategies. Four (M1-M4) were identified from rat urine by sensitive method with...
Objective Chronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) dihydroxyeicosatrienoic (DHETs). We undertook this study assess whether EH–driven metabolism EETs DHETs plays critical role in chronic joint associated...
Soluble epoxide hydrolase (sEH) inhibitors function to stabilize biologically active lipid metabolites responsible for regulating homeostatic biological processes. The presence of these beneficial in tissues and their metabolism by sEH into less diols was first reported 30 years ago, many subsequent advances were facilitated several academic laboratories, principally University California at Davis. These efforts led the identification a large chemical library potent inhibitors. Researchers...
A highly sensitive biotinylated IgG–streptavidin-polyHRP label-based ELISA for detection of linoleic acid-derived diols in human plasma.
There are few novel therapeutic options available for companion animals, and medications rely heavily on repurposed drugs developed other species. Considering the diversity of species breeds in animal medicine, comprehensive PK exposures patient is often lacking. The purpose this paper was to assess pharmacokinetics after oral intravenous dosing domesticated (dogs, cats, horses) a soluble epoxide hydrolase inhibitor, EC1728, being treatment pain animals. Results: Intravenous administration...
Abstract Background Although high‐throughput DNA/RNA sequencing technologies have generated massive genetic and genomic data in human disease, translation of these findings into new patient treatment has not materialized by lack effective approaches, such as Artificial Intelligence (AL) Machine Learning (ML) tools. Method To address this problem, we used AI/ML Mendelian randomization (MR), large patient’s functional to evaluate druggable targets using Alzheimer’s disease (AD) a prototypical...
Activation of Ca2+-independent phospholipase A2β (iPLA2β) leads to production proinflammatory prostaglandins E2 (PGE2) and diols generated by cyclooxygenase (COX) soluble epoxide hydrolase (sEH), respectively, we reported that decreasing iPLA2β reduces T1D incidence. Importantly, find inhibiting PGE2 signaling with an EP4r antagonist or sEH inhibitor mitigates immune cell inflammatory phenotype. We therefore tested if (with grapiprant, GP) &lt;u&gt;EC&lt;/u&gt;5026) can...
Abstract Background Although investment in biomedical and pharmaceutical research has increased significantly over the past two decades, there are no oral disease‐modifying treatments for Alzheimer’s disease (AD). Method We performed comprehensive human genetic multi‐omics data analyses to test likely causal relationship between EPHX2 (encoding soluble epoxide hydrolase [sEH]) risk of AD. Next, we tested effect administration EC5026 (a first‐in‐class, picomolar sEH inhibitor) a transgenic...
Inhibition of soluble epoxide hydrolase (sEHI) was shown to be potent reduce the inflammation, lower blood pressure in hypertension and is being developed for indication chronic pain treatment. Guiding by vitro potency screening, pharmacokinetics vivo efficacy studies, a sEHI (EC5026) optimized followed clinical trials. Besides its own properties, formulation method an important factor considered reach ideal exposure time span concentration , therefore . Here, we compared three different...