urb-597 and Colitis

urb-597 has been researched along with Colitis* in 3 studies

Other Studies

3 other study(ies) available for urb-597 and Colitis

ArticleYear
Switching cannabinoid response from CB(2) agonists to FAAH inhibitors.
    Bioorganic & medicinal chemistry letters, 2014, Mar-01, Volume: 24, Issue:5

    A series of 3-carboxamido-5-aryl-isoxazoles designed as CB2 agonists were evaluated as FAAH inhibitors. The pharmacological results led to identify structure-activity relationships enabling to switch cannabinoid response from CB2 agonists to FAAH inhibitors. Two compounds were selected for their FAAH and/or CB2 activity, and evaluated in a colitis model for their anti-inflammatory activity. Results showed that compounds 10 and 11 inhibit the development of DSS-induced acute colitis in mice and then, are interesting leads to explore new drug candidates for IBD.

    Topics: Adamantane; Amidohydrolases; Animals; Anti-Inflammatory Agents; Body Weight; Cannabinoids; Colitis; Disease Models, Animal; Enzyme Inhibitors; Isoxazoles; Male; Mice; Mice, Inbred C57BL; Protein Binding; Receptor, Cannabinoid, CB2; Structure-Activity Relationship

2014
New FAAH inhibitors based on 3-carboxamido-5-aryl-isoxazole scaffold that protect against experimental colitis.
    Bioorganic & medicinal chemistry, 2011, Jun-15, Volume: 19, Issue:12

    Growing evidence suggests a role for the endocannabinoid (EC) system, in intestinal inflammation and compounds inhibiting anandamide degradation offer a promising therapeutic option for the treatment of inflammatory bowel diseases. In this paper, we report the first series of carboxamides derivatives possessing FAAH inhibitory activities. Among them, compound 39 displayed significant inhibitory FAAH activity (IC(50)=0.088 μM) and reduced colitis induced by intrarectal administration of TNBS.

    Topics: Amidohydrolases; Animals; Colitis; Disease Models, Animal; Enzyme Activation; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Isoxazoles; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Structure

2011
Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors.
    Journal of molecular medicine (Berlin, Germany), 2008, Volume: 86, Issue:8

    The endocannabinoid (EC) system mediates protection against intestinal inflammation. In this study, we investigated the effects of blocking EC degradation or cellular reuptake in experimental colitis in mice. Mice were treated with trinitrobenzene-sulfonic acid in presence and absence of the fatty acid amide hydrolase (FAAH) blocker URB597, the EC membrane transport inhibitor VDM11, and combinations of both. Inflammation was significantly reduced in the presence of URB597, VDM11, or both as evaluated by macroscopic damage score, myeloperoxidase levels, and colon length. These effects were abolished in CB(1)- and CB(2)-receptor-gene-deficient mice. Quantitative reverse transcription polymerase chain reaction after induction of experimental colitis by different pathways showed that expression of FAAH messenger RNA (mRNA) is significantly reduced in different models of inflammation early in the expression of colitis, and these return to control levels as the disease progresses. Genomic DNA from 202 patients with Crohn's disease (CD) and 206 healthy controls was analyzed for the C385A polymorphism in the FAAH gene to address a possible role in humans. In our groups, the C385A polymorphism was equally distributed in patients with CD and healthy controls. In conclusion, drugs targeting EC degradation offer therapeutic potential in the treatment of inflammatory bowel diseases. Furthermore, reduction of FAAH mRNA expression is involved in the pathophysiological response to colitis.

    Topics: Amidohydrolases; Animals; Arachidonic Acids; Benzamides; Cannabinoid Receptor Modulators; Carbamates; Colitis; Crohn Disease; Disease Models, Animal; Endocannabinoids; Humans; Mice; Mice, Inbred C57BL; Polymorphism, Genetic; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Messenger; Trinitrobenzenesulfonic Acid

2008