HE 3286

HE3286, a synthetic derivative of the adrenal steroid β-AET, is an orally-active partially NF-κB inhibitor [1][2].

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

HE3286 attenuates NF-κB phosphorylation, but not influences IκB phosphorylation of LPS-induces (100 ng/ml; 0-2 hours) murine macrophages [3]. HE3286 (100 nM, overnight) partially, but significantly, blocks the activation of IKK, JNK, p38, and ERK of LPS-induces (100 ng/ml; 0-2 hours) murine macrophages[3]. Western Blot Analysis[3] Cell Line: LPS-induced murine macrophages Concentration: 100 nM Incubation Time: overnight Result: Attenuated NF-κB phosphorylation. Blocked the activation of IKK, JNK, p38, and ERK partially, but significantly.

HE3286 (80 mg/kg; 0-24h) freely penetrates the BBB in male CD-1 mice[4]. HE3286 (40 mg/kg; gavage; twice-daily for 4 days) increases the numbers of tyrosine hydroxylase-positive cells and decreases the numbers of damaged neurons in PD mice [4]. HE3286 (40 mg/kg; intraperitoneal injection; daily for 40 days) suppresses inflammation, reduces demyelination and axonal loss, and promotes RGC survival during experimental optic neuritis of EAE mice [2]. HE3286 (25-50 mg/kg; oral gavage; daily for 22-49 days) reduces joint inflammation, synovial proliferation, and erosion of DBA/1 Lac male CIA mice [1].

[1]. [1] Auci D, et al. A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells. Ann N Y Acad Sci. 2007;1110:630-640.

[2]. [2] Khan RS, et al. HE3286 reduces axonal loss and preserves retinal ganglion cell function in experimental optic neuritis. Invest Ophthalmol Vis Sci. 2014;55(9):5744-5751. Published 2014 Aug 19.

[3]. [3] Lu M,et al. A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. Am J Physiol Endocrinol Metab. 2010;298(5):E1036-E1048.

[4]. [4] Nicoletti F, et al. 17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) Is Neuroprotective and Reduces Motor Impairment and Neuroinflammation in a Murine MPTP Model of Parkinson's Disease. Parkinsons Dis. 2012;2012:969418.