The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3β,17β-androstenediol, and testosterone in human serum using gas chromatography–mass spectrometry

Hill, Martin; Havlı́ková, Helena; Vrbíková, Jana; Kancheva, Radmila; Kancheva, Lyudmila; Pouzar, Vladimı́r; Černý, Ivan; Stárka, L.

doi:10.1016/j.jsbmb.2005.02.009

Cited by 22 publications

(11 citation statements)

References 45 publications

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“…Androstene-3 β , 7 β , 17 β- triol ( β- AET) is biosynthesized from DHEA, biologically active in rodents [29-32] and naturally occurring in humans [33-37]. It's functions in the body may include tissue-specific modulation of glucocorticoid (GC) action, immune function, and control of acute and chronic inflammation [38-40].…”

Section: Introductionmentioning

confidence: 99%

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

et al. 2010

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Background17α-Ethynyl-5-androsten-3β, 7β, 17β-triol (HE3286) is a synthetic derivative of an endogenous steroid androstenetriol (β-AET), a metabolite of the abundant adrenal steroid deyhdroepiandrosterone (DHEA), with broad anti-inflammatory activities. We tested the ability of this novel synthetic steroid with improved pharmacological properties to limit non-productive lung inflammation in rodents and attempted to gauge its immunological impact.Methods and ResultsIn mice, oral treatment with HE3286 (40 mg/kg) significantly (p < 0.05) decreased neutrophil counts and exudate volumes (~50%) in carrageenan-induced pleurisy, and myeloperoxidase in lipopolysaccharide-induced lung injury. HE3286 (40 mg/kg) was not found to be profoundly immune suppressive in any of the classical animal models of immune function, including those used to evaluate antigen specific immune responses in vivo (ovalbumin immunization). When mice treated for two weeks with HE3286 were challenged with K. pneumoniae, nearly identical survival kinetics were observed in vehicle-treated, HE3286-treated and untreated groups.ConclusionsHE3286 represents a novel, first-in-class anti-inflammatory agent that may translate certain benefits of β-AET observed in rodents into treatments for chronic inflammatory pulmonary disease.

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Section: Introductionmentioning

confidence: 99%

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

et al. 2010

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“…Although androstene‐3β, 7β, 17β‐triol (β‐AET) is readily detected in rodents receiving exogenous DHEA, β‐AET is absent or present in very low levels without DHEA supplementation. β‐AET is naturally present in humans 19 …”

Section: Introductionmentioning

confidence: 99%

HE3286: A Novel Synthetic Steroid as an Oral Treatment for Autoimmune Disease

Ahlem

Auci

Mangano

et al. 2009

Annals of the New York Academy of Sciences

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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.

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“…We hypothesized that these oxygenated DHEA metabolites were responsible for activities attributed to DHEA in rodents. Androstene-3␤,7␤,17␤-triol (AET) was described previously (Butenandt et al, 1938;Reynolds, 1966) as a more highly oxygenated natural DHEA metabolite found in humans (Hill et al, 2005) that provided anti-inflammatory benefit in animal models of autoimmunity and trauma (Offner et al, 2002;Auci et al, 2003;Marcu et al, 2006). However, metabolic instability and poor oral bioavailability of AET suggested limited pharmaceutical usefulness of this natural hormone (Hollis-Eden Pharmaceuticals Inc., unpublished observations).…”

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confidence: 99%

An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis

Offner

Firestein

Boyle

et al. 2009

J Pharmacol Exp Ther

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The identification and simultaneous quantification of 7-hydroxylated metabolites of pregnenolone, dehydroepiandrosterone, 3β,17β-androstenediol, and testosterone in human serum using gas chromatography–mass spectrometry

Cited by 22 publications

References 45 publications

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

HE3286, an oral synthetic steroid, treats lung inflammation in mice without immune suppression

HE3286: A Novel Synthetic Steroid as an Oral Treatment for Autoimmune Disease

An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis

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