基于高浓度电生理学的片段筛选：新型酸感应离子通道 3（ASIC3）抑制剂的发现。
High concentration electrophysiology-based fragment screen: discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors.
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, Sumneytown Pike, PO Box 4, West Point, PA 19486, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 1;21(9):2646-9. doi: 10.1016/j.bmcl.2010.12.115. Epub 2010 Dec 28.
PMID:21257308
Abstract
The Merck Fragment Library was screened versus acid-sensing ion channel 3 (ASIC3), a novel target for the treatment of pain. Fragment hits were optimized using two strategies, and potency was improved from 0.7 mM to 3 μM with retention of good ligand efficiency and incorporation of reasonable physical properties, off-target profile, and rat pharmacokinetics.
摘要
默克片段库针对酸感应离子通道 3（ASIC3）进行了筛选，这是一种治疗疼痛的新型靶点。使用两种策略对片段进行了优化，在保留良好配体效率的同时，将效力从 0.7mM 提高到 3μM，并具有合理的物理性质、非靶点特征和大鼠药代动力学。
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