Whitty Adrian, Riera Thomas V
Department of Chemistry, Boston University, Metcalf Center for Science and Engineering, 590 Commonwealth Avenue, Boston, MA 02215-2521, USA.
Curr Opin Chem Biol. 2008 Aug;12(4):427-33. doi: 10.1016/j.cbpa.2008.05.014. Epub 2008 Jun 18.
Numerous important drugs target cytokines and growth factors or their receptors. Our understanding of the molecular mechanisms governing receptor activation and signaling has lagged in key areas, however, limiting drug discovery efforts to relatively few basic strategies. Recently, substantial progress has been made on several aspects of this problem. These include improved methods for establishing the mechanism of receptor activation, a clearer understanding of the biochemical basis for differential signaling by ligands that act through a common receptor, new methods for measuring the affinities of steps in receptor activation on live cells, and progress toward a systems level understanding of receptor signaling. These advances are providing a new understanding of the function of these receptors that presents opportunities for the development of improved drugs.
许多重要药物作用于细胞因子、生长因子或其受体。然而，我们对受体激活和信号传导分子机制的理解在关键领域仍存在滞后，这使得药物研发工作局限于相对较少的基本策略。最近，在该问题的几个方面取得了重大进展。这些进展包括建立受体激活机制的改进方法、对通过共同受体起作用的配体差异信号传导生化基础的更清晰理解、测量活细胞上受体激活步骤亲和力的新方法，以及在系统层面理解受体信号传导方面取得的进展。这些进展为这些受体的功能提供了新的认识，为开发改进药物带来了机遇。
