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类固醇激素受体与药物发现:治疗机遇与检测方法设计

Steroid hormone receptors and drug discovery: therapeutic opportunities and assay designs.

作者信息

Bai Chang, Schmidt Azriel, Freedman Leonard P

机构信息

Department of Molecular Endocrinology, Merck Research Laboratories, West Point, PA 19486-0004, USA.

出版信息

Assay Drug Dev Technol. 2003 Dec;1(6):843-52. doi: 10.1089/154065803772613471.

Abstract

Steroid receptors belong to the nuclear hormone receptor superfamily, which represents one of the important families of drug targets in the pharmaceutical industry. These receptors are generally expressed in a broad range of tissues and play roles in multiple physiological pathways. They represent one of the most complex target classes for drug research as the typical pharmacologically selective, potent, and pure agonist or antagonist may not be sufficient for the development of an optimal compound for therapeutic use. In many cases, the professed compound that is a selective modulator of a steroid hormone receptor that functions as an agonist in one tissue and as an antagonist in another can offer a better therapeutic advantage. In this review, we will selectively summarize members of the steroid hormone receptor subfamily, their therapeutic opportunities, and a glimpse of the methods that can be utilized in the development of drugs that target these receptors.

摘要

类固醇受体属于核激素受体超家族,该超家族是制药行业中重要的药物靶点家族之一。这些受体通常在广泛的组织中表达,并在多种生理途径中发挥作用。它们是药物研究中最复杂的靶点类别之一,因为典型的具有药理选择性、强效且纯的激动剂或拮抗剂可能不足以开发出用于治疗的最佳化合物。在许多情况下,宣称的化合物作为类固醇激素受体的选择性调节剂,在一个组织中起激动剂作用而在另一个组织中起拮抗剂作用,可能会提供更好的治疗优势。在本综述中,我们将选择性地总结类固醇激素受体亚家族的成员、它们的治疗机会,以及对可用于开发靶向这些受体的药物的方法的简要介绍。

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