Schäcke Heike, Rehwinkel Hartmut, Asadullah Khusru
Schering AG, RBA Dermatology Europe, 13342 Berlin, Germany.
Curr Opin Investig Drugs. 2005 May;6(5):503-7.
Glucocorticoids are well known for their potent anti-inflammatory and immunosuppressive actions. However, due to their potential to induce serious undesired effects, there is a great need for compounds with a better therapeutic index. Recent discoveries have demonstrated that the positive and negative regulation of gene expression via the glucocorticoid receptor is mediated by different mechanisms. This regulation is predominantly responsible for either anti-inflammatory effects or certain side effects, depending on whether it is negative or positive. Compounds that preferentially induce transrepression rather than transactivation should be superior to classical glucocorticoids. Indeed, proof of concept has been recently achieved with such selective glucocorticoid receptor agonists.
糖皮质激素以其强大的抗炎和免疫抑制作用而闻名。然而，由于它们有可能引发严重的不良影响，因此迫切需要具有更好治疗指数的化合物。最近的研究发现表明，糖皮质激素受体对基因表达的正负调控是由不同机制介导的。这种调控主要负责抗炎作用或某些副作用，具体取决于它是负调控还是正调控。优先诱导反式抑制而非反式激活的化合物应该优于传统的糖皮质激素。事实上，最近已经通过这类选择性糖皮质激素受体激动剂实现了概念验证。
