title: 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.
authors.affiliation: HollisEden Pharmaceuticals, San Diego, CA, USA.
authors.forename: Dominick L
authors.initials: DL
authors.lastname: Auci
authors.forename: Katia
authors.initials: K
authors.lastname: Mangano
authors.forename: Daniel
authors.initials: D
authors.lastname: Destiche
authors.forename: Steven K
authors.initials: SK
authors.lastname: White
authors.forename: Yujin
authors.initials: Y
authors.lastname: Huang
authors.forename: David
authors.initials: D
authors.lastname: Boyle
authors.forename: James
authors.initials: J
authors.lastname: Frincke
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Reading
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D001835:Body Weight; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D029822:Enterovirus B, Human / Q000502:physiology; D006801:Humans; D007114:Immunization; D015850:Interleukin-6 / Q000097:blood; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D009205:Myocarditis / Q000188:drug therapy / Q000821:virology; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C524733:17-ethynyl-5-androstene-3, 7, 17-triol; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003687:Dehydroepiandrosterone; D009195:Peroxidase