School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
Future Med Chem. 2009 May;1(2):345-59. doi: 10.4155/fmc.09.21.
Endogenous glucocorticoids (GCs) are involved in a range of endocrine functions including the metabolism of lipids, carbohydrates and proteins, stress response, fluid and electrolyte balance, as well as the maintenance of immunological, renal and skeletal homeostasis. There is a need to find agents that preserve the immune effects of GCs without side effects such as those affecting metabolism (diabetes), bone tissue (osteoporosis), muscles (myopathy), eyes and skin.
In this review, we focus on the use of recent computational approaches in glucocorticoid receptor (GR) drug-design efforts for the determination of novel GR ligands. We examine a number of structure-based (e.g., homology modeling and docking) studies that have been implemented and evaluate their success.
By the end of 2008, there had been limited achievements utilizing docking studies and no published successes in the area of virtual high-throughput screening. However, the availability of novel crystal structures and the use of induced-fit docking protocols are improving docking success rates and promising to aid the future delivery of nonsteroidal ligands.
内源性糖皮质激素（GCs）参与多种内分泌功能，包括脂质、碳水化合物和蛋白质代谢、应激反应、体液和电解质平衡以及维持免疫、肾脏和骨骼内环境稳定。因此，人们需要寻找既能保留 GC 的免疫作用，又没有代谢（糖尿病）、骨骼组织（骨质疏松症）、肌肉（肌病）、眼睛和皮肤等副作用的药物。
在这篇综述中，我们重点介绍了使用最近的计算方法进行糖皮质激素受体（GR）药物设计，以确定新型 GR 配体。我们研究了一些基于结构的（例如，同源建模和对接）研究，并评估了它们的成功。
截至 2008 年底，利用对接研究的成果有限，在虚拟高通量筛选领域也没有成功的案例。然而，新型晶体结构的出现和诱导契合对接方案的使用正在提高对接成功率，并有望为未来提供非甾体配体提供帮助。
