The Cyclofluidic Approach

Small molecule lead discovery involves an iterative process of molecular design, chemical synthesis, biological assay and analysis to feed into the next learning cycle. In a typical hit to lead project a range of assays are required to measure the potency and selectivity of the molecule at the target of interest as well as a range of calculated and measured physical properties that help to predict a lead molecule's "drug-likeness". Using conventional approaches, each learning cycle in this process takes 1-8 weeks, depending on where compounds are made and tested. These cycle times lead to slow and expensive hit to lead exploration, limiting the number of hit series that can be assessed. In addition, compounds are often designed and made "at risk" i.e. without incorporating the latest data from the previous design cycles, leading to wasted effort and resource.

The Cyclofluidic technology platform integrates all these processes allowing drug lead molecules to be assayed minutes rather than weeks after they are designed. Potential lead molecules are synthesised, purified and screened in fast serial mode, incorporating activity data from each compound as it is generated before selecting the next compound to make.

Each compound is purified by integrated high pressure liquid chromatography (HPLC), its identity confirmed by mass spectrometry and the concentration entering the assay determined in real time by evaporative light scattering detection (ELSD). The compound's IC₅₀ is then measured in the on-line biochemical assay and this result fed into the design selection algorithm before the algorithm selects the next compound to make. The system is designed to use interchangeable design algorithms, assay formats and chemistries and at any stage a medicinal chemist can adjust the design strategy through the flexible user interface.