LASSBio Chemical Library: molecular properties profile and repurposing studies

The LASSBio Chemical Library (LCL) contains ca. 2300 compounds, and the library content selection has been driven by medicinal chemistry concepts.1,2 This work describes content characterization of the LCL, and virtual screening against lysine-specific demethylase 1 (LSD1), and fms like tyrosine kinase 3 (FLT-3), targets relevant for the treatment of acute myeloid leukemia.
Chemical diversity analysis of LCL was performed in KNIME platform, and led to the identification of main chemotypes of the LCL. Preliminarily pharmacokinetic (PK) profile was determined using Percepta (ACD/Labs, 2012), and showed that 85% of its compounds are compliant with Lipinski's Ro5. Virtual screening led to the selection 17 substances for pharmacological assays. LASSBio-1000 and LASSBio-2166 inhibited 46% (LSD1) and 87% (FLT3) of enzymatic activity at 10 µM concentration, respectively. These compounds may represent a starting point for subsequent design of dual inhibitors of these enzymes.