The University of Kansas HTS Laboratory currently has 4 commercial libraries available for screening. The libraries are stored in sealed, 384-well microtiter plates at -20°C. The compounds are stored in 100%DMSO at a concentration of 1 mg/mL. The compounds are transferred to assay plates prior to screening at an assay dependent concentration. We generally screen 80 compounds in 96-well format and 320 compounds in a 384-well format. For assay validation, the MicroSource and Prestwick Libraries are screened to ensure assay performance.
We purchased the compounds from ChemBridge Corp. (San Diego, CA), and the compounds were selected from their Express-Pick collection of 450,000 compounds. In addition to consideration of the Lipinski rule, we also drew upon the vast drug discovery experience of professors at the Medicinal Chemistry Department of University of Kansas in the selection process. Reactive, unstable and potentially toxic compounds, such as esters, amides, acid chlorides, Michael acceptors, and poly-aromatics were eliminated, and all compounds are solids with molecular weight between 150 and 480 and cLogP below 5. This is a library of compounds that was optimized for structural diversity and drug-like properties.
We applied the same strict criteria for selecting compounds from a large collection of compounds from ChemDiv, Inc. (San Diego, CA). We paid special attention to purchase compounds with complementary properties and different structural scaffolds compared to the ChemBridge compounds.
The Prestwick Chemical's (Illkirch, France) library is a unique collection of 1120 off-patent small organic molecules, 90% being marketed drugs and 10% bioactive alkaloids or related substances. The compounds are carefully selected for their structural diversity, broad spectrum activity covering several therapeutic areas (from neuropsychiatry to cardiology, immunology, anti-inflammatory, analgesia and more) and for their known safety and bioavailability profiles in humans.
The 2000 compounds from the Spectrum collection of MicroSource Discovery Systems, Inc. (Gaylordsville, CT) encompass a wide range of biological activities and structural diversity for screening programs. Approximately 50% of the library consists of drugs that have been introduced into the United States, Europe and Japan. They have known pharmacological and toxicological profiles that have been published. Natural products with unknown biological properties make up 30% of the library and the remaining 20% of the compounds are other bioactive representatives such as non-drug enzyme inhibitors, receptor blockers, membrane active compounds, and cellular toxins that have not reached development or are toxic.
The legacy library is a continually expanding set of compounds by researchers in the KU Medicinal chemistry and Chemistry departments. The University of Kansas Center of Excellence in Chemical Methodologies & Library Development (KU CMLD) has synthesized libraries utilizing new principles of scaffold design. The compounds have drug-like characteristics and pharmacological activity based on established drug design principles.
