Biodiversity of small molecules - a new perspective in screening set selection

详细信息    查看全文

• 作者：Paula M. Petrone ; Anne Mai Wassermann ; Eugen Lounkine ; Peter Kutchukian ; Benjamin Simms ; Jeremy Jenkins ; Paul Selzer ; Meir Glick
• 刊名：Drug Discovery Today
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：18
• 期：13-14
• 页码：674-680
• 全文大小：709 K

文摘

How is the ¡®diversity¡¯ of a compound set defined and how is the most appropriate compound subset identified for assay when screening the entire HTS deck is not an option? A common approach has so far been to cover as much of the chemical space as possible by screening a chemically diverse set of compounds. We show that, rather than chemical diversity, the biologic diversity of a compound library is an essential requirement for hit identification. We describe a simple and efficient approach for the design of a HTS library based on compound-target diversity. Biodiverse compound subsets outperform chemically diverse libraries regarding hit rate and the total number of unique chemical scaffolds present among hits. Specifically, by screening ¡«19 % of a HTS collection, we expect to discover ¡«50-80 % of all desired bioactive compounds.