Goldmann Daria, Pakfeifer Peter, Hering Steffen, Ecker Gerhard F
University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
Future Med Chem. 2015;7(3):243-56. doi: 10.4155/fmc.14.168.
The transient receptor potential vanilloid type 1 (TRPV1) is responsible for pain perception in the peripheral nervous system (PNS). TRPV1 is thus considered a versatile target for development of non-opioid analgesics.
Pharmacophore-based clustering of a publicly available data set of TRPV1 antagonists revealed a set of models, which were validated with data sets of inactive compounds, decoys and known drug candidates. The top ranked pharmacophore models were subsequently used for virtual screening. Based on a unique in-house protocol, a set of compounds was selected and biologically tested for modulation of TRPV1 in a voltage-clamp model.
Pharmacophore models extracted from large public data sets are a valuable source for identification of novel scaffolds for TRPV1 receptor modulation.
瞬时受体电位香草酸亚型1（TRPV1）在外周神经系统（PNS）中负责痛觉感知。因此，TRPV1被认为是开发非阿片类镇痛药的一个通用靶点。
基于药效团对公开可用的TRPV1拮抗剂数据集进行聚类，得到了一组模型，这些模型用非活性化合物、诱饵和已知药物候选物的数据集进行了验证。随后，排名靠前的药效团模型被用于虚拟筛选。基于一个独特的内部方案，选择了一组化合物，并在电压钳模型中对其调节TRPV1的作用进行了生物学测试。
从大型公共数据集中提取的药效团模型是识别用于TRPV1受体调节的新型骨架的宝贵来源。
