Small Molecule Screening Core

Small Molecule Screening Core (SMSC) provides the researchers at CCF and other biomedical research centers in Cleveland area with the expertise, technology, instrumentation and reagents necessary for the screening of the library of small molecules for biologically active compounds in a variety of readout systems. The core can provide help with the adjustment of readout systems for both cell-based and biochemical assays and establishment of screening conditions based on a pilot small-scale screening. (For more information about analysis of screening data please follow the Helpful information link of this site). If successful, the established system is used for a full-scale library screening in 96-well format followed by generation of the database with the results. SMSC also offers help with data processing and planning further steps in optimization of isolated chemicals, including primary chemoinformatics analysis, generation of virtual libraries of analogues and consulting on the tactics of compound characterization, including connection with outside partners. Outline of the services provided by the core is presented at the flowchart graphic.

Chemical library and instrumentation

SMSC owns the diverse historical chemical library of 34,000 compounds manufactured by Chembridge Corporation, world recognized leader in this field. The library consists of handcrafted drug-like organic molecules with molecular weight in a range of 250 - 550, which were dissolved in DMSO at concentration 5mg/ml or 10-20 mM depending on molecular weight. Their structure and >95% purity have been validated by NMR. The library is formatted in 96-well format with 80 compounds per plate (16 wells contain only DMSO and can be used for controls).

Core's equipment allows preparation and maintenance of cultures of reporter cells, plating them in mutiwell format (Multidrop 384, Thermo/Labsystems) and collection of data in a variety of formats (Wallac 1420 VICTOR2 multilabel reader). Additionally SMSC can assist in generation and analysis of screening databases and provide additional information on the properties of selected hits (cytotoxicity, etc.).

Relevant publications:

• Komarov et al. (1999). A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 285, 1733-1777.
• Kondratov et al. (2001). Small molecules that dramatically alter the substrate specificity of P-glycoprotein multidrug transporter. PNAS 98, 14078-14083.
• Gurova et al. (2005). Small molecules, reactivating p53 in renal cell carcinoma, reveal a new NF-kB-dependent mechanism of p53 suppression in tumors. PNAS 102, 17448-17453.
• Thakur CS et al. (2007). Small-molecule activators of RNase L with broad-spectrum antiviral activity. PNAS104(23), 9585-9590.