4 research outputs found
Additional file 2: of A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis
Figure S1. Hierarchical clustering analysis revealed differential expression of circulating microRNAs between lean and 3H mice in an independent study (study 2). (DOCX 347Ă‚Â kb
Additional file 1: of A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis
Table S1. Complete list of microRNAs analyzed. (DOCX 17Ă‚Â kb
Additional file 3: of A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis
Figure S2. Time-dependent expression of miR-122, miR-192, miR-21, miR-29a, miR-34a, and miR-505 in study 1. Data were expressed as minus delta Ct with reference to spike-in control miRNA. (DOCX 149Ă‚Â kb
Discovery of Clinical Candidate 2‑((2<i>S</i>,6<i>S</i>)‑2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3′-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor
BMS-816336
(<b>6n-2</b>), a hydroxy-substituted adamantyl
acetamide, has been identified as a novel, potent inhibitor against
human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)
enzyme (IC<sub>50</sub> 3.0 nM) with >10000-fold selectivity over
human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). <b>6n-2</b> exhibits a robust acute pharmacodynamic effect in cynomolgus
monkeys (ED<sub>50</sub> 0.12 mg/kg) and in DIO mice. It is orally
bioavailable (%<i>F</i> ranges from 20 to 72% in preclinical
species) and has a predicted pharmacokinetic profile of a high peak
to trough ratio and short half-life in humans. This ADME profile met
our selection criteria for once daily administration, targeting robust
inhibition of 11β-HSD1 enzyme for the first 12 h period after
dosing followed by an “inhibition holiday” so that the
potential for hypothalamic–pituitary–adrenal (HPA) axis
activation might be mitigated. <b>6n-2</b> was found to be well-tolerated
in phase 1 clinical studies and represents a potential new treatment
for type 2 diabetes, metabolic syndrome, and other human diseases
modulated by glucocorticoid control