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Iso‐maleimycin, a previously unknown constitutional isomer of the antibiotic maleimycin, has been detected in an extract of Streptomyces sp. QL37. Chemical synthesis of both maleimycin (20 % yield over seven steps) and iso‐maleimycin, (15 % yield over six steps) allowed access to reference materials for identification. Gas Chromatography coupled Mass Spectrometry (GC‐MS) analysis demonstrated that of the two isomers, only iso‐maleimycin was present in the extract. This finding supports our hypothesis that iso‐maleimycin is a biosynthetic intermediate of lugdunomycin. Iso‐maleimycin displays low antibiotic activity, with a Minimum Inhibitory Concentration (MIC) value on both E. coli and B. subtilis of 250 µg/mL. [ABSTRACT FROM AUTHOR]

R3613 --> 856.4 --> Objective: This study investigates the protective properties of farsenoid X receptor (FXR) agonism by the drug Obeticholic Acid (OCA) in the adenine‐induced tubulointerstitial fibrosis model of kidney disease male and female mice. Hypothesis: OCA treatment will decrease the expression of SMAD3 and phosphorylated‐SMAD3, and therefore will be nephroprotective in the adenine model of kidney disease in male and female mice. Methods: Male and female C57BL/6J mice (12 weeks old) were fed chow (Research Diets D1912040li) or chow admixed with adenine (0.2% w/w) ad lib for 7 weeks. Mice were treated with either vehicle (corn oil) or obeticholic acid (10 mg/kg BW) by gavage 5 days per week. Plasma and organs were collected and processed for bio‐chemical analysis. Results: OCA treatment reduced BUN and plasma creatinine in diseased mice of both sexes. FXR agonism reduced SMAD3 expression in both male (P<0.05) and female (P<0.05) mice. Importantly, FXR agonism also reduced SMAD3 phosphorylation in both male (P<0.05) and female (P<0.001) mice. On histology, OCA reduced renal fibrosis in male (P<0.05) but not female mice. Conclusions: FXR agonism by OCA is anti‐fibrotic in the adenine model of tubulointerstitial fibrotic crystalline nephropathy in male and female mice. Mechanistically, OCA prevents renal fibrosis by reducing SMAD3 expression and phosphorylation. [ABSTRACT FROM AUTHOR]