| 蒋明黄思罗林昕春雷皮振钧孙兵张文华赵菡刘剑峰.GABAB 受体变构剂药学研究进展[J].,2011,11(14):2775-2778 |
| GABAB 受体变构剂药学研究进展 |
| The Progress of Pharmacology of GABAB Receptors Allosteric Modulators |
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| DOI： |
| 中文关键词: GABAB 受体 药物靶点 变构剂 药物开发 筛选模型 |
| 英文关键词: GABAB receptors Drug target Allosteric modulators Drug development Screening model |
| 基金项目:国家科技部国家重大科学研究计划蛋白质专项子课题(2007CB914202) |
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| 中文摘要: |
| γ- 氨基丁酸B 受体(GABAB receptor, GABABR) 是最具有药理学意义的药物靶点之一，具有复杂而精细的激活机制。传统
的GABABR 靶点药物开发集中于激动剂和拮抗剂，这类药物受到多种因素的制约，包括较强的副作用、药物代谢困难、机体耐药
性明显等。变构剂结合于正构位点之外，能够调节GABABR 异源二聚体亚基或结构域间的相互作用。正向变构剂（positive
allosteric modulators，PAMs）和负向变构剂（negative allosteric modulators，NAMs）分别可以提高或降低GABABR 的活性，并具有较
高的特异性和药物安全性，同时还能够保持GABABR 信号在时间和空间上的可控性。变构剂为GABABR 靶点药物开发提供了新
思路。 |
| 英文摘要: |
| GABAB receptors are a member of the G protein-coupled family of receptors which are generally considered to be
excellent drug targets, with a complex and refined mechanism of activation. Traditional drug development targeted at GABAB receptors is
focused on agonists and antagonists, the use of which is limited by its side effects, poor pharmacokinetics, and the development of tolerance.
Allosteric modulators, which interact with binding sites topologically distinct from the orthosteric ligand binding sites, can modulate
the interaction between subunits or domains in the GABAB heterodimer. Positive and negative allosteric modulators can potentiate or
decrease the activity of GABAB receptors respectively, with improved selectivity and safety, along with maintenance of spatial and temporal
aspects of GABAB receptors signaling. Allosteric modulators give the new opportunity on the GABAB receptors targeted drug development. |
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