title: HE3286: a novel synthetic steroid as an oral treatment for autoimmune disease.
abstract: HE3286 (17alpha-ethynyl-5-androstene-3beta, 7beta, 17beta-triol) is a synthetic derivative of a natural anti-inflammatory steroid, beta-AET (5-androstene-3beta, 7beta, 17beta-triol). HE3286 is orally bioavailable and treats established disease in models of ulcerative colitis, collagen-induced arthritis, and collagen antibody-induced arthritis, reducing clinical signs of disease and proinflammatory signals, including IL-6 and matrix metallopeptidase 3. HE3286 modulates nuclear factor kappaB through an unknown mechanism but does not interact with any of the steroid-binding nuclear hormone receptors and is not immune suppressive. HE3286 was safe and well tolerated in phase I studies and is under evaluation in multicenter phase I/II clinical trials for ulcerative colitis and arthritis. HE3286 may provide a new treatment option for patients with inflammatory and autoimmune diseases.
authors.affiliation: Hollis-Eden Pharmaceuticals, San Diego, California 92121, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ahlem
authors.forename: D
authors.initials: D
authors.lastname: Auci
authors.forename: K
authors.initials: K
authors.lastname: Mangano
authors.forename: C
authors.initials: C
authors.lastname: Reading
authors.forename: J
authors.initials: J
authors.lastname: Frincke
authors.forename: D
authors.initials: D
authors.lastname: Stickney
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000284:Administration, Oral; D000737:Androstenols / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: C524733:17-ethynyl-5-androstene-3, 7, 17-triol; C108492:5-androstene-3,7,17-triol; D000737:Androstenols; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D003687:Dehydroepiandrosterone; D004958:Estradiol