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Oral treatment with HE3286 ameliorates disease in rodent models of rheumatoid arthritis.

Abstract
HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is an orally bio-available synthetic derivative of naturally occurring androstene-3beta, 7beta, 17beta-triol. Our present data show that oral treatment with HE3286, favourably influenced the course of arthritis in the rat model of adjuvant-induced arthritis (reduced cumulative disease scores and paw edema), and in the mouse model of collagen antibody-induced arthritis (reduced clinical paw scores). Importantly, HE3286 was not immune suppressive in human mixed lymphocyte reaction or in animals challenged with Coxsackie B3 virus. HE3286 is currently in phase I/II clinical trials in rheumatoid arthritis and ulcerative colitis and these findings further strengthen the possibility that HE3286 may represent an effective anti-inflammatory agent useful for treating chronic inflammation with a more attractive safety profile than glucocorticoids or cyclooxygenase inhibitors.
AuthorsDominick L Auci, Katia Mangano, Daniel Destiche, Steven K White, Yujin Huang, David Boyle, James Frincke, Christopher L Reading, Ferdinando Nicoletti
JournalInternational journal of molecular medicine (Int J Mol Med) Vol. 25 Issue 4 Pg. 625-33 (Apr 2010) ISSN: 1791-244X [Electronic] Greece
PMID20198312 (Publication Type: Journal Article)
Chemical References
  • 17-ethynyl-5-androstene-3, 7, 17-triol
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Dehydroepiandrosterone
  • Peroxidase
Topics
  • Administration, Oral
  • Animals
  • Arthritis, Experimental (blood, drug therapy, enzymology, pathology)
  • Arthritis, Rheumatoid (blood, drug therapy, enzymology, pathology)
  • Body Weight
  • Dehydroepiandrosterone (administration & dosage, analogs & derivatives, pharmacology, therapeutic use)
  • Disease Models, Animal
  • Disease Progression
  • Enterovirus B, Human (physiology)
  • Humans
  • Immunization
  • Interleukin-6 (blood)
  • Lymphocyte Culture Test, Mixed
  • Male
  • Mice
  • Myocarditis (drug therapy, virology)
  • Organ Size
  • Peroxidase (metabolism)
  • Rats
  • Time Factors
  • Tumor Necrosis Factor-alpha (blood)

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