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Cell Res:中科院上海药物所徐华强课题组基于结构研发的哮喘候选新药取得进展

摘要 : 2015年12月15日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表中国科学院上海药物所徐华强研究组与美国Van Andel研究所的研究人员展开合作发表的哮喘候选新药研究论文

 2015年12月15日,国际学术权威刊物自然出版集团旗下子刊《Cell Research》杂志在线发表中国科学院上海药物所徐华强研究组与美国Van Andel研究所的研究人员展开合作发表的哮喘候选新药研究论文,上海药物所的徐华强研究员、易伟副研究员和美国Van Andel研究所Yuanzheng He博士为该论文的共同通讯作者。

哮喘作为人体常见呼吸道疾病之一,已成为仅次于癌症的世界第二大致死和致残疾病。近年来哮喘患病人数因各种原因逐年上升,使得这一问题更不容忽视。糖皮质激素受体(Glucocortiucoids receptor,GR)是一个开发治疗哮喘药物的热门靶标。至今,以其为靶点开发的糖皮质激素类药物如fluticasone furoate已作为当今最为有效的治疗哮喘药物被广泛地应用于市场中,然而大量的临床实验表明糖皮质激素类药物具有非常大的副作用,长期使用会导致肥胖症、糖尿病、骨质疏松、皮肤萎缩等多种不良反应。因此,开发一种高效、结构新颖、毒副作用低的新型治疗哮喘药物,已成为当今医学和药学领域中的关键问题之一。

中国科学院上海药物研究所徐华强研究组与美国Van Andel研究所的研究人员展开合作,基于前期的工作基础,进一步设计合成了一系列具有明显靶向特征的新型糖皮质激素。从先导化合物体VSG-22成功发现高效化合物VSG-C12, 体内外的测试结果显示,VSG-C12活性是当今市场上哮喘药物fluticasone furoate(FF)的4倍,同时在有效浓度下显示出比FF较小的毒副作用。

原文链接:

Discovery of a highly potent glucocorticoid for asthma treatment

原文摘要:

Glucocorticoids are the most effective treatment for asthma. However, their clinical applications are limited by low efficacy in severe asthma and by undesired side effects associated with high dose or prolonged use. The most successful approach to overcome these limitations has been the development of highly potent glucocorticoids that can be delivered to the lungs by inhalation to achieve local efficacy with minimal systemic effects. On the basis of our previous structural studies, we designed and developed a highly potent glucocorticoid, VSGC12, which showed an improved anti-inflammation activity in both cell-based reporter assays and cytokine inhibition experiments, as well as in a gene expression profiling of mouse macrophage RAW264.7 cells. In a mouse asthma model, VSGC12 delivered a higher efficacy than fluticasone furoate, a leading clinical compound, in many categories including histology and the number of differentiated immune cells. VSGC12 also showed a higher potency than fluticasone furoate in repressing most asthma symptoms. Finally, VSGC12 showed a better side effect profile than fluticasone furoate at their respective effective doses, including better insulin response and less bone loss in an animal model. The excellent therapeutic and side effect properties of VSGC12 provide a promising perspective for developing this potent glucocorticoid as a new effective drug for asthma.

来源: Cell Research 浏览次数:0

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