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.

中文翻译：

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发现了用于哮喘治疗的高效糖皮质激素。

糖皮质激素是治疗哮喘最有效的方法。但是，它们的临床应用受到严重哮喘的低效治疗以及与高剂量或长期使用相关的不良副作用的限制。克服这些局限性的最成功方法是开发可通过吸入传递至肺部的高效糖皮质激素，以达到局部功效而将全身作用降至最低。在我们之前的结构研究的基础上，我们设计和开发了一种高效的糖皮质激素VSGC12，在基于细胞的报告基因检测和细胞因子抑制实验以及小鼠的基因表达谱分析中均显示出改善的抗炎活性。巨噬细胞RAW264.7细胞。在小鼠哮喘模型中，VSGC12比糠酸氟替卡松具有更高的疗效，领先的临床化合物，包括组织学和分化的免疫细胞数量在内的许多类别。VSGC12在抑制大多数哮喘症状方面也显示出比糠酸氟替卡松更高的效力。最后，在动物模型中，VSGC12在其各自的有效剂量下比糠酸氟替卡松具有更好的副作用，包括更好的胰岛素反应和更少的骨质流失。VSGC12出色的治疗和副作用特性为开发这种有效的糖皮质激素作为哮喘的新有效药物提供了广阔的前景。在动物模型中，VSGC12在其各自的有效剂量下比糠酸氟替卡松具有更好的副作用，包括更好的胰岛素反应和更少的骨质流失。VSGC12出色的治疗和副作用特性为开发这种有效的糖皮质激素作为哮喘的新有效药物提供了广阔的前景。在动物模型中，VSGC12在其各自的有效剂量下比糠酸氟替卡松具有更好的副作用，包括更好的胰岛素反应和更少的骨质流失。VSGC12出色的治疗和副作用特性为开发这种有效的糖皮质激素作为哮喘的新有效药物提供了广阔的前景。