Diversity-Oriented Synthesis as a Strategy for Fragment Evolution against GSK3β

作者：Yikai Wang, Jean-Yves Wach, Patrick Sheehan, Cheng Zhong, Chenyang Zhan, Richard Harris, Steven C. Almo, Joshua A. Bishop, Stephen J. Haggarty, Alexander Ramek, Kayla N. Berry, Conor O’Herin, Angela N. Koehler, Alvin W. Hung, Damian W. Young · 发表于：ACS Medicinal Chemistry Letters · 年份：2016 · DOI：10.1021/acsmedchemlett.6b00230 · 被引用次数：39 · 研究领域：Cancer-related gene regulation、Ubiquitin and proteasome pathways、PI3K/AKT/mTOR signaling in cancer

Traditional fragment-based drug discovery (FBDD) relies heavily on structural analysis of the hits bound to their targets. Herein, we present a complementary approach based on diversity-oriented synthesis (DOS). A DOS-based fragment collection was able to produce initial hit compounds against the target GSK3β, allow the systematic synthesis of related fragment analogues to explore fragment-level structure-activity relationship, and finally lead to the synthesis of a more potent compound.