Dmd063339 788..802
نویسندگان
چکیده
Dr. Bernard Brodie’s legacy is built on fundamental discoveries in pharmacology and drug metabolism that were then translated to the clinic to improve patient care. Similarly, the development of a novel class of therapeutics termed the soluble epoxide hydrolase (sEH) inhibitors was originally spurred by fundamental research exploring the biochemistry and physiology of the sEH. Here, we present an overview of the history and current state of research on epoxide hydrolases, specifically focusing on sEHs. In doing so, we start with the translational project studying the metabolism of the insect juvenile hormone mimic R-20458 [(E)-6,7-epoxy-1-(4ethylphenoxy)-3,7-dimethyl-2-octene], which led to the identification of the mammalian sEH. Further investigation of this enzyme and its substrates, including the epoxyeicosatrienoic acids, led to insight into mechanisms of inflammation, chronic and neuropathic pain, angiogenesis, and other physiologic processes. This basic knowledge in turn led to the development of potent inhibitors of the sEH that are promising therapeutics for pain, hypertension, chronic obstructive pulmonary disorder, arthritis, and other disorders.
منابع مشابه
microRNA-802 inhibits epithelial-mesenchymal transition through targeting flotillin-2 in human prostate cancer
miRNAs are a class of non-coding RNAs that exert critical roles in various biological processes. The aim of the present study was to identify the functional roles of miR-802 in regulating epithelial-mesenchymal transition (EMT) in prostate cancer (PCa). miR-802 expression was detected in 73 pairs of PCa samples and PCa cell lines (PC3 and DU145 cells) by qRT-PCR. Cell proliferation was detected...
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microRNAs play important roles in numerous biological processes, including tumorigenesis, by modulating critical gene transcripts. In the present study, the role of microRNA‑802 (miR‑802) in lung cancer was investigated. The results of the quantitative polymerase chain reaction revealed that expression levels of miR‑802 were significantly upregulated in lung cancer tissues. In vitro experiments...
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The antimicrobial activity of flumequine (R-802) was characterized by in vitro and in vivo procedures. Assay of the minimal inhibitory concentrations for 321 recent clinical isolates revealed that 88% of the gram-negative bacteria were inhibited by an R-802 concentration of 6.2 mug/ml or less. Cross-resistance in laboratory-derived mutants of Proteus vulgaris was essentially complete for R-802,...
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Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in left carotid and were treated with CP-96345 (NK1 antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or presence ...
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