HTS follow-up using JChem Base; virtual and vendor neighbors
There is always intense pressure to move rapidly from 'hits' in a primary screen to optimization on validated leads. In this, informatics personnel need to worry, not just about presenting screening data in a useful way (using clustering for example), but framing those hits in the context of literature compounds, identifying related commercially-available compounds, and capturing and organizing the plethora of follow-up ideas from chemists. In particular, the unique challenges posed by the management of virtual and commercial compound databases with several million entries has lead us to design and implementation heuristics that facilitate the rapid, dynamically tunable identification of compounds using substructure, 'lead-like' and chemical filters. For the medicinal chemists on the project team, following-up HTS hits is an opportunity to think creatively. Tracking and sharing chemists' ideas (virtual compounds) and commercially-available compounds, interactively filling SAR gaps with those same compounds and visualizing project data in a multiplexed fashion are techniques we will discuss in this talk for encouraging that creativity.