Article
Cardiac & Cardiovascular Systems
Chengcheng Zhao, Xiangrui Jiang, Liyuan Peng, Yan Zhang, Huihui Li, Qiumeng Zhang, Yinhui Wang, Feipu Yang, Junfang Wu, Zheng Wen, Zuowen He, Jingshan Shen, Chen Chen, Dao Wen Wang
Summary: This study found that the ratio of DHETs/EETs increased in the plasma of heart failure (HF) patients, and the expression of sEH was upregulated in the heart of patients and mice with HF. Cardiomyocyte-specific Ephx2-/- mice showed improved cardiac dysfunction induced by TAC. Mechanistically, AngII enhanced the expression of KLF15, which in turn upregulated sEH. Importantly, glimepiride was identified as a novel sEH inhibitor that attenuated HF by increasing EETs.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Article
Cell Biology
Ahmed A. El-Sherbeni, Rabia Bhatti, Fadumo A. Isse, Ayman O. S. El-Kadi
Summary: This study identified two compounds that simultaneously inhibit the activity of MMP and sEH, which could provide a promising intervention for the prevention and control of diseases, especially cardiovascular diseases.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2022)
Article
Cell Biology
Matthieu Leuillier, Valentin Platel, Ly Tu, Guillaume Feugray, Raphael Thuillet, Deborah Groussard, Hind Messaoudi, Mina Ottaviani, Mustapha Chelgham, Lionel Nicol, Paul Mulder, Marc Humbert, Vincent Richard, Christophe Morisseau, Valery Brunel, Thomas Duflot, Christophe Guignabert, Jeremy Bellien
Summary: Inhibitors of soluble epoxide hydrolase (sEH) present an opportunity for developing oral drugs for cardiovascular and inflammatory diseases. However, the administration of sEH inhibitors may lead to the development of pulmonary hypertension (PH). This study evaluated the impact of chronic oral administration of the sEH inhibitor TPPU on hemodynamics and pulmonary vascular remodeling in rats. The results showed that TPPU did not induce or aggravate PH and RV dysfunction, and may have a potential beneficial effect against pulmonary artery remodeling in humans.
Article
Food Science & Technology
Cheng-Peng Sun, Xin-Yue Zhang, Jun-Jun Zhou, Xiao-Kui Huo, Zhen-Long Yu, Christophe Morisseau, Bruce D. Hammock, Xiao-Chi Ma
Summary: The study evaluated the important role of sEH in AD mice, revealing that sEH inhibitors can alleviate learning and memory deficits, elevate neurotransmitter levels, and exert anti-AD effects through regulating multiple signaling pathways.
FOOD AND CHEMICAL TOXICOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shinichiro Koike, Ming-Fo Hsu, Ahmed Bettaieb, Bryan Chu, Naoki Matsumoto, Christophe Morisseau, Peter J. Havel, Mark O. Huising, Bruce D. Hammock, Fawaz G. Haj
Summary: The study identified that upregulation of soluble epoxide hydrolase (sEH) expression in beta-cells under diet-induced metabolic stress could lead to beta-cell dysfunction. Genetic deficiency of sEH enhanced glucose-stimulated insulin secretion in mice, improving systemic glucose control and reducing oxidative stress and beta-cell death. Inhibition of sEH showed potential in mitigating high fat diet-induced beta-cell loss and dedifferentiation.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Physiology
Mi Ra Noh, Hee-Seong Jang, Fadi E. Salem, Fernando A. Ferrer, Jinu Kim, Babu J. Padanilam
Summary: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that have various biological effects. Recent studies have shown that inhibiting the enzyme soluble epoxide hydrolase (sEH) can prevent kidney fibrosis and inflammation. This study investigates the use of EET regioisomers and sEH inhibition to promote antifibrotic and renoprotective effects in renal fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Article
Cell Biology
Menglu Fu, Jing Yu, Zhihui Chen, Ying Tang, Ruolan Dong, Yan Yang, Jinlan Luo, Shuiqing Hu, Ling Tu, Xizhen Xu
Summary: Studies have shown that epoxyeicosatrienoic acids (EETs) have a positive effect on regulating glucose homeostasis in diabetic states by reducing glucose reabsorption and suppressing the expression of SGLT2. Additionally, EETs can ameliorate insulin resistance and diabetes by preventing NF-κB-mediated transcription of SGLT2.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Physiology
Agnieszka Walkowska, Ludek Cervenka, John D. Imig, John R. Falck, Janusz Sadowski, Elzbieta Kompanowska-Jezierska
Summary: The study demonstrated that in spontaneously hypertensive rats, both EET-A and AAA induced renal vasodilation but did not show additive effects. Both agents have a definite therapeutic potential for hypertension and deserve further experimental and clinical testing for novel antihypertensive therapy.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Huiyi Yang, Meng Qi, Qiyi He, Sung Hee Hwang, Jun Yang, Mark Mccoy, Christophe Morisseau, Suqing Zhao, Bruce D. Hammock
Summary: This study developed a nanobody-based enzyme-linked immunosorbent assay (ELISA) for accurate quantification of drug compounds. The assay showed excellent correlation with liquid chromatography mass spectrometry (LC-MS) analysis and can be easily implemented for monitoring small molecule medicines during clinical development and therapy.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)
Review
Immunology
Wei Tao, Gang Xu, Yi Luo, Ping-Song Li
Summary: This study investigated the effects of sEH inhibitors on ALI using meta-analysis. The results showed that sEH inhibitors can reduce lung injury scores and lung wet to dry weight ratios in animal models. The study also found that the mortality rate was improved by sEH inhibitors after 48 hours, 72 hours, and 120 hours, but not at 24 hours and 96 hours.
INFLAMMOPHARMACOLOGY
(2022)
Article
Engineering, Environmental
Juan Zhang, Wen-Hao Zhang, Christophe Morisseau, Min Zhang, Hong-Jun Dong, Qi-Meng Zhu, Xiao-Kui Huo, Cheng-Peng Sun, Bruce D. Hammock, Xiao-Chi Ma
Summary: PM2.5 is closely related to respiratory diseases and lung inflammation. sEH and epoxy fatty acids play a vital role in this inflammation. In a mouse model of PM2.5-mediated lung injury, the cytochrome P450 oxidase/sEH metabolic pathway was found to be involved. The inhibition of sEH protected against lung injury by increasing levels of EETs and inactivating pulmonary macrophages.
JOURNAL OF HAZARDOUS MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Matthew L. Edin, Artiom Gruzdev, J. Alyce Bradbury, Joan P. Graves, Fred B. Lih, Laura M. DeGraff, Ingrid Fleming, Darryl C. Zeldin
Summary: The specific role of EPHX2 in cardiac cell types was investigated. The study found that EPHX2 expression and activity are highest in cardiomyocytes, and lower in endothelial cells. Specific disruption of EPHX2 in cardiomyocytes led to significantly reduced expression and hydrolase activity, and enhanced postischemic cardiac function.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Vladimir Burmistrov, Christophe Morisseau, Dmitry Pitushkin, Robert R. Fayzullin, Dmitry Karlov, Andrey Vernigora, Yaroslav Kuznetsov, Saeef M. H. Abbas, Gennady M. Butov, Bruce D. Hammock
Summary: The study found that ureas derived from t-camphor exhibited higher activity against sEH, while ureas derived from fenchone showed lower activity. The compound L-3a derived from t-camphor showed greater potency in inhibiting sEH compared to its counterpart derived from m-camphor.
RESULTS IN CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Karen M. Wagner, Jun Yang, Christophe Morisseau, Bruce D. Hammock
Summary: The soluble epoxide hydrolase (sEH) enzyme regulates bioactive lipids, with its activity affected more by high-fat diets in male mice than in female mice. High-fat diets increase sEH activity, prostaglandins, and triglycerides in male mice, but these effects are limited by sEH knockout. Similar changes occur in female mice but to a different degree and are also improved by sEH enzyme knockout.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wen-Yu Zhao, Xin-Yue Zhang, Mei-Rong Zhou, Xiang-Ge Tian, Xia Lv, Hou-Li Zhang, Sa Deng, Bao-Jing Zhang, Cheng-Peng Sun, Xiao-Chi Ma
Summary: The inhibition of soluble epoxide hydrolase (sEH) is considered an effective treatment for inflammation-related diseases. Two novel sEH inhibitors were identified from Alisma orientate, providing potential leads for the development of sEH inhibitors based on protostane-type triterpenoids. In-depth studies revealed the mechanism of inhibition and highlighted the role of amino acid residue Ser374 in the activity of the inhibitors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemical Research Methods
Anil K. Padyana, Bhamini Vaidialingam, David B. Hayes, Priyanka Gupta, Michael Franti, Neil A. Farrow
ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Xiang Li, Marie Anderson, Delphine Collin, Ingo Muegge, John Wan, Debra Brennan, Stanley Kugler, Donna Terenzio, Charles Kennedy, Siqi Lin, Mark E. Labadia, Brian Cook, Robert Hughes, Neil A. Farrow
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Alexander Heim-Riether, Steven J. Taylor, Shuang Liang, Donghong Amy Gao, Zhaoming Xiong, E. Michael August, Brandon K. Collins, Bennett T. Farmer, Kathleen Haverty, Melissa Hill-Drzewi, Hans-Dieter Junker, S. Mariana Margarit, Neil Moss, Thomas Neumann, John R. Proudfoot, Lana Smith Keenan, Renate Sekul, Qiang Zhang, Jun Li, Neil A. Farrow
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2009)
Article
Chemistry, Medicinal
Anne B. Eldrup, Fariba Soleymanzadeh, Neil A. Farrow, Alison Kukulka, Stephane De Lombaert
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Donghong Amy Gao, Zhaoming Xiong, Alexander Heim-Riether, Laura Amodeo, E. Michael August, Xianhua Cao, Leonard Ciccarelli, Brandon K. Collins, Kyle Harrington, Kathleen Haverty, Melissa Hill-Drzewi, Xiang Li, Shuang Liang, Steluta Mariana Margarit, Neil Moss, Nelamangala Nagaraja, John Proudfoot, Rene Roman, Sabine Schlyer, Lana Smith Keenan, Steven Taylor, Bernd Wellenzohn, Dieter Wiedenmayer, Jun Li, Neil A. Farrow
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Ho Yin Lo, Chuk C. Man, Roman W. Fleck, Neil A. Farrow, Richard H. Ingraham, Alison Kukulka, John R. Proudfoot, Raj Betageri, Tom Kirrane, Usha Patel, Rajiv Sharma, Mary Ann Hoermann, Alisa Kabcenell, Stephane De Lombaert
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2010)
Article
Chemistry, Medicinal
Ho Yin Lo, Peter A. Nemoto, Jin Mi Kim, Ming-Hong Hao, Kevin C. Qian, Neil A. Farrow, Daniel R. Albaugh, Danielle M. Fowler, Richard D. Schneiderman, E. Michael August, Leslie Martin, Melissa Hill-Drzewi, Steven S. Pullen, Hidenori Takahashi, Stephane De Lombaert
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Medicinal
Steven J. Taylor, Asitha Abeywardane, Shuang Liang, Ingo Muegge, Anil K. Padyana, Zhaoming Xiong, Melissa Hill-Drzewi, Bennett Farmer, Xiang Li, Brandon Collins, John Xiang Li, Alexander Heim-Riether, John Proudfoot, Qiang Zhang, Daniel Goldberg, Ljiljana Zuvela-Jelaska, Hani Zaher, Jun Li, Neil A. Farrow
JOURNAL OF MEDICINAL CHEMISTRY
(2011)
Article
Biochemistry & Molecular Biology
Eric T. Larson, Debra L. Brennan, Eugene R. Hickey, Raj Ganesan, Rachel Kroe-Barrett, Neil A. Farrow
Article
Multidisciplinary Sciences
PH Carter, PA Scherle, JA Muckelbauer, ME Voss, RQ Liu, LA Thompson, AJ Tebben, KA Solomon, YC Lo, Z Li, P Strzemienski, GJ Yang, N Falahatpisheh, M Xu, ZR Wu, NA Farrow, K Ramnarayan, J Wang, D Rideout, V Yalamoori, P Domaille, DJ Underwood, JM Trzaskos, SM Friedman, RC Newton, CP Decicco
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2001)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
