Identification of novel serotonin 2C receptor ligands by sequential virtual screening
Identification of novel serotonin 2C receptor ligands by sequential virtual screening
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DOI：
10.1016/j.bmc.2009.05.003
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发表时间：
2009-07-01
影响因子：
3.5
通讯作者：
Pae, Ae Nim
中科院分区：
文献类型：
--
作者：
Ahmed, Asif;Choo, Hyunah;Pae, Ae Nim
药效团建模、对接和虚拟筛选已成为药物发现过程中的重要工具。5-羟色胺2C（5-HT 2C）受体配体作为抗抑郁剂和厌食剂的治疗用途受到了广泛关注。使用5-HT 2C激动剂进行基于药效团和对接的两步虚拟筛选。两个共同的特征药效团定向虚拟命中具有亚微摩尔活性。构建了具有排除体积的精炼药效团，并与基于同源性模型的对接相结合。来自该虚拟筛选的最佳命中显示IC 50为20.1 nM。该命中化合物的相似性搜索得到具有7.8nM活性的更有活性的配体。(C)2009爱思唯尔有限公司保留所有权利。
Pharmacophore modelling, docking and virtual screening have become important tool in drug discovery process. Serotonin 2C (5-HT2C) receptor ligands have got major attention for their therapeutic uses as antidepressant and anorectic agents. Two step pharmacophore and docking based virtual screening was done using 5-HT2C agonists. Two common feature pharmacophore directed virtual hits had submicromolar activity. Refined pharmacophore with excluded volumes was constructed and combined with homology model based docking. Best hit from this virtual screening showed IC50 of 20.1 nM. Similarity search of this hit compound resulted more active ligand with 7.8 nM activity. (C) 2009 Elsevier Ltd. All rights reserved.