Tehan Benjamin G, Christopher John A
Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, United Kingdom.
Heptares Therapeutics, Biopark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, United Kingdom.
Curr Opin Pharmacol. 2016 Oct;30:8-13. doi: 10.1016/j.coph.2016.06.010. Epub 2016 Jul 9.
Recent developments in receptor stabilisation have facilitated major advances in G protein-coupled receptor (GPCR) research, notably structural biology, over the past eight years. Here we review the application of fragment, structure and biophysical techniques using stabilised GPCRs (StaR proteins), and their impact in the drug discovery process. These techniques have, most recently, been utilised in the discovery of the non-alkyne mGlu negative allosteric modulator HTL14242, in addition to the dual orexin receptor antagonist HTL6641, with differentiated residence time kinetics.
在过去八年中，受体稳定化方面的最新进展推动了G蛋白偶联受体（GPCR）研究取得重大进展，尤其是在结构生物学领域。本文中，我们综述了使用稳定化GPCR（StaR蛋白）的片段、结构和生物物理技术的应用，以及它们在药物发现过程中的影响。除了具有不同驻留时间动力学的双重食欲素受体拮抗剂HTL6641外，这些技术最近还被用于发现非炔基代谢型谷氨酸受体负变构调节剂HTL14242。
