7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases

Auci, Dominick L.; Reading, Christopher L.; Frincke, James M.

doi:10.1016/j.autrev.2008.11.011

Cited by 38 publications

(40 citation statements)

References 36 publications

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“…In addition, we show herein that HE3286 was not immune suppressive in MLR studies and that extended pre-treatments were safe and may even have provided benefit in the murine model of myocarditis induced by CB3V infection. The present studies confirm the anti-inflammatory activity reported for HE3286 in our previous publications (23,24,26).…”

Section: Discussionsupporting

confidence: 81%

“…Our previous studies with AET showed benefit in rodent models of ulcerative colitis and multiple sclerosis (23,24). Thus, a broad based anti-inflammatory activity is perhaps central to the activities of HE3286 in auto-immune disease.…”

Section: Discussionmentioning

confidence: 97%

“…The 7-hydroxyated metabolites of DHEA retain potent anti-inflammatory and immune modulating activity but are practically devoid of unwanted side effects (reviewed in ref. 23). Previously we showed that subcutaneous (s.c) injection of androstene-3ß, 7ß, 17ß-triol (AET) provided benefit in rodent models of ulcerative colitis (24) and experimental autoimmune encephalitis (25).…”

Section: Introductionmentioning

confidence: 99%

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

Nicoletti¹

2010

Int J Mol Med

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Abstract. 7ß, is an orally bio-available synthetic derivative of naturally occurring androstene-3ß, 7ß, 17ß-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 antiinflammatory agent useful for treating chronic inflammation with a more attractive safety profile than glucocorticoids or cyclooxygenase inhibitors.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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

Nicoletti¹

2010

Int J Mol Med

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“…However, later on it has been established that at the cellular level, irreversible 7α-hydroxylation of 3ß-hydroxy-5-ene steroids produces derivatives, which are believed to be responsible for at least some immunity-promoting and antiglucocorticoid effects (Morfin and Courchay, 1994;Hampl et al, 2000;Morfin et al, 2000;Morfin, 2002;Auci et al, 2009). As "neuroprotective steroids" and immunity promoters in the brain, 7α-hydroxy-steroids could contribute to the panels of cellular protection and defense (Morfin and Stárka, 2001;Dušková et al, 2011).…”

mentioning

confidence: 99%

7-oxygenated Derivatives of Dehydroepiandrosterone and Obesity

et al. 2012

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7-hydroxy/oxo derivatives of dehydroepiandrosterone are potential regulators of the local cortisol activity due to their competition in the cortisolcortisone balance mediated by 11ß-hydroxysteroid dehydrogenase. 7-hydroxydehydroepiandrosterone is marketed as anti-obesity medication, though no clinical study aimed at the benefit of administering 7-oxygenated derivatives of dehydroepiandrosterone has appeared until now. We tried to show whether there exist differences in levels of circulating 7-hydroxy/oxo-dehydroepiandrosterone derivatives between lean and obese boys and girls. From a cohort of adolescents investigated within the frame of anti-obesity programme 10 obese boys and 10 obese girls were compared with age-matched lean boys and girls in their anthropometric data, and concentrations of both epimers of 7-hydroxydehydroepiandrosterone and 7-oxo-dehydroepiandrosterone were determined by the RIA method. The basal levels of 7α-hydroxy-dehydroepiandrosterone were significantly higher in obese boys than in lean boys but not in girls. The association was found for anthropometric parameters and 7α-hydroxy-dehydroepiandrosterone, however again only in boys and not in girls. Higher levels of 7α-hydroxydehydroepiandrosterone its positive association with anthropometric data in obese boys may serve as a sign that, at least in boys, 7-oxygenated 5-ene-steroids may take part in regulating the hormonal signal for fat formation or distribution. Financial Mechanisms, and NT 12342-5/2011 This study was supported by grants: NS/9831-4 of the Internal Grant Agency of the Ministry of Health of the Czech Republic, CZ0123 from Norway through the Norwegian

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“…Steroidal compounds display a variety of biological [1][2][3] functions and play a very important role in life [4][5][6], and attracted profound attention for development of potent pharmacological agents for treatments of various diseases [7] including: cardiovascular disease [8], adrenal insufficiencies [9], autoimmune disorders [10], fungal and microbial infections [11,12]. Furthermore, different steroidal derivatives have been considered as potent anti-cancer agents for the treatment of leukemia [7], breast cancer [13][14][15], prostate cancer [16] and brain tumors [17].…”

Section: Introductionmentioning

confidence: 99%

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

2015

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A new series of (5-pregnen-20-on-3α-yl)-substituted-benzoate analogues (10-13), (5-pregnene-20-on-3α-yl)-3-(substituted)acrylate derivatives (17-19) as well as the (17-(2-acetoxyacetyl)pregen-3α-yl)-3,4,5-trihydroxybenzoate (21) were synthesized from the β-pregenenolone scaffolds, by applying Mitsunobu reaction. All new compounds were characterized by 1 H, 13 C and 2D NMR spectroscopy. The inversion in configuration at C-3 during the formation of α-ester analogues was confirmed by NOESY NMR spectroscopy. The new compounds were evaluated for their in vitro antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. Compounds 18 showed an EC50 value of >1.95 mg/mL. In addition, preliminary structure-activity relationship and molecular modeling of compound 18 has been studied.

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7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases

Cited by 38 publications

References 36 publications

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

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

7-oxygenated Derivatives of Dehydroepiandrosterone and Obesity

Exploration of new 3α-pregnenolone ester analogues via Mitsunobu reaction, their anti-HIV activity and molecular modeling study

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