AvalonRx®
Biomarker based Lead Optimization
Lead optimization seeks to improve the attractive bioactivities of initial hits from primary screens, while minimizing or removing detrimental compound characteristics. Optimization is most often achieved via lead explosion, when hundreds of new analogs are examined in an iterative fashion. This part of the AvalonRx® system is supported by a set of cheminformatics tools focused on examining compounds in the context of transcriptional data.

Investigation of Structure-Activity Relationships (SAR) is a fundamental activity carried out by medicinal chemists during the process of optimization of hits to lead compounds. It allows for the recognition of correlations between structures of tested compounds and their biological activity. At Avalon, we take advantage of the additional source of molecular interaction data provided by expression biomarkers. We conduct our SAR studies with a focus on the ability of the hits and their analogs to effect gene signatures representative of "on target" and "off target" effects, often prior to any knowledge about physical compound targets. This process of Transcriptional Structure-Activity Relationship (termed TSAR) permits simultaneous optimization of potency, and most importantly of selectivity.

Avalon's unique TSAR approach provides a rapid way to analyze candidate drugs at the lead optimization stage. In the TSAR process, transcriptional effects guide compound optimization, and compounds are ranked according to gene expression, magnitude and selectivity of transcriptional effects as well as other biological and chemical properties. The most promising compounds are advanced to further testing to assess their potential as drug candidates.