生物谷报道：糖皮质激素是最有效地，也是使用最广泛的抗炎药物之一，但它的巨大副作用一直制约临床的应用，人类一直在探索新型的抗炎药物。由辉瑞公司等多家公司的科学家组成的San Diego配体药物开发研究小组最近发现一种有望替代糖皮质激素作为抗炎药物的新型药物。
糖皮质激素是最为有效地抗炎药物，但是它不仅能抑制主要的炎症相关基因的表达，同时它还能抑制许多其它的基因表达，如免疫系统中许多免疫因子基因的表达，从而产生免疫抑制等许多副作用。这一小组针对糖皮质激素受体（glucocorticoid receptor ，GR）的配体，开发出一系列药物，其中最为有效的成分为LGD5552，它不仅能与GR受体强烈地结合，而且能抑制炎症基因的表达，但是它并不影响其它的基因表达，因此，它能达到抗炎却不伤及“无辜”的效果。生物谷专家认为，这一研究成果，给人类开发抗炎药物提供了新型思路，它有望成为安全地替代糖皮质激素的抗炎药物，如果该型药物开发成果，将开创强效炎症抑制药物的新时代。
Glucocorticoids are commonly used antiinflammatory agents whose use is limited by side effects. We have developed a series of glucocorticoid receptor (GR) ligands that retain the strong antiinflammatory activity of conventional glucocorticoids with reduced side effects. We present a compound, LGD5552, that binds the receptor efficiently and strongly represses inflammatory gene expression. LGD5552 bound to GR activates gene expression somewhat differently than glucocorticoids. It activates some genes with an efficacy similar to that of the glucocorticoids. However, other glucocorticoid-activated genes are not regulated by LGD5552. These differences may be because of the more efficient binding of corepressor in the presence of LGD5552, compared with glucocorticoid agonists. This class of nonsteroidal, GR-dependent antiinflammatory drugs may offer a safer alternative to steroidal glucocorticoids in the treatment of inflammatory disease.
原始出处：
Jeffrey N. Miner, Bob Ardecky, Khalid Benbatoul, Kimberly Griffiths, Christopher J. Larson, Dale E. Mais, Keith Marschke, Jon Rosen, Eric Vajda, Lin Zhi, and Andres Negro-Vilar
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