HE3286, an orally bioavailable synthetic analogue of an active DHEA metabolite suppresses spontaneous autoimmune diabetes in the non-obese diabetic (NOD) mouse

Michele M. Kosiewicz, Dominick L. Auci, Paolo Fagone, Katia Mangano, Salvatore Caponnetto, Colleen F. Tucker, Nabeel Azeem, Steven K. White, James M. Frincke, Christopher L. Reading, Ferdinando Nicoletti

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

5-Androstene-3β,7β,17β-triol (AET) is a naturally occurring anti-inflammatory adrenal steroid that limits acute and chronic inflammation. HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol) is a synthetic derivative of AET with improved pharmaceutical properties and efficacy in some animal models of autoimmunity. Here, daily oral doses of HE3286 led to a suppression of spontaneous autoimmune diabetes in the non-obese diabetic mouse model of type 1 diabetes mellitus when administered either shortly before or after the first incidence of disease onset. Efficacy was associated with reduced insulitis and a suppression of the pathogenic T helper cell type 1 and type 17 phenotypes in peripheral lymphoid organs. These results demonstrate that daily oral treatment with HE3286 administrated relatively late in the destructive autoimmune process led to a suppression of type 1 diabetes mellitus onset and of the pathological inflammatory status, supporting its clinical evaluation in type 1 diabetes mellitus subjects.

Original languageEnglish (US)
Pages (from-to)257-262
Number of pages6
JournalEuropean Journal of Pharmacology
Volume658
Issue number2-3
DOIs
StatePublished - May 11 2011

Keywords

  • Androstene
  • Diabetes
  • IL-17
  • NOD
  • Steroid

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