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口服 HE3286 可改善类风湿关节炎啮齿动物模型的疾病。

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

机构信息

HollisEden Pharmaceuticals, San Diego, CA, USA.

出版信息

Int J Mol Med. 2010 Apr;25(4):625-33. doi: 10.3892/ijmm_00000385.

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.

摘要

HE3286(17α-乙炔基-5-雄烯-3β,7β,17β-三醇)是一种可口服生物利用的天然雄烯-3β,7β,17β-三醇的合成衍生物。我们目前的数据表明,口服 HE3286 可改善佐剂诱导性关节炎大鼠模型(降低累积疾病评分和爪肿胀)和胶原抗体诱导性关节炎小鼠模型(降低临床爪评分)的关节炎病程。重要的是,HE3286 在人混合淋巴细胞反应或柯萨奇 B3 病毒攻击的动物中没有免疫抑制作用。HE3286 目前正在类风湿关节炎和溃疡性结肠炎的 I/II 期临床试验中,这些发现进一步增强了这样一种可能性,即 HE3286 可能代表一种有效的抗炎剂,可用于治疗慢性炎症,其安全性比糖皮质激素或环氧化酶抑制剂更具吸引力。

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