Wide-range solubility characterization per compound, modality-agnostic at the framework level. Small molecules, peptides, PROTACs, MCPs, miniproteins — same workflow.
High-throughput assessment of compound solubility, powered by Ultrafast Light Scattering (ULS)
A plate-based workflow on ORYL F1, using Linear Light Scattering (LLS)
Louis Dumas1, Aristea Massaras1, Orly Tarun1
1ORYL Photonics SA, Route de la Corniche 5B, 1066 Epalinges, Switzerland
Summary
Solubility remains a discovery bottleneck as hit lists expand, molecules become more complex, and early screening increasingly includes new modalities. This application note describes a high-throughput, low-compound, plate-based workflow on ORYL F1 for compound solubility assessment using Linear Light Scattering (LLS), within the broader ORYL Ultrafast Light Scattering (ULS) platform. Starting from 10 mM DMSO stock solutions, compounds were prepared in a 384-well format, diluted into PBS pH 7.4, incubated for 24 h with shaking, measured on ORYL F1 using ORYL Screener software, and analyzed in ORYL Analyzer to generate LLS-derived solubility profiles, LLS-derived solubility limits, and confidence intervals. Once plates are ready, the 384 wells can be measured in 15 minutes.
Data is shown for a discovery-triage panel comprising three standard small molecules, three peptides, and three PROTACs, each tested in 11- or 12-point concentration series with three replicate wells. The results illustrate the type of decision-ready output obtained from the F1 workflow across diverse compound classes, including new modalities. For Albendazole, Dipyridamole, and Caffeine, HPLC-MS derived reference values are available and match our LLS-derived solubility limits, providing a focused external credibility anchor for the workflow.