SMDC
Small Molecule Discovery Center
Cherry Picking

After screening data has been processed and deposited in our database, compounds are prioritized for re-supply for the user lab to confirm the hits and to generate an initial dose response curve. Similar to other academic screening centers, we re-supply a maximum of 0.3% of the total number of compounds screened.

The criteria for choosing a hit is based on the initial potency scored in the primary screen, the lack of interference effects displayed by the compound under screening conditions, the lack of known toxic effects associated with the compound, and the lack of promiscuous non-specific activity demonstrated by the compound in other screens we have run.

After the list of recommended cherry pick hits has been generated, we re-supply 5 µL of 5 mM stocks in 100% DMSO for each compound chosen.

Further characterization of hits in secondary screens requires the use of milligram amounts of compounds. Many of the compounds in our collection can be re-ordered in milligram quantities by user labs from the original vendor at reasonable prices.

Two resources we routinely use to search for re-supply availability and compound analogs are ZINC and Scifinder. Zinc is a database created by John Irwin and is a free resource for locating suppliers of commercially available compounds. Also, for UCSF screeners, Scifinder can be downloaded and can also be used to source commercial compounds. In addition, both Zinc and Scifinder can search for analogs of hits, allowing user labs to begin SAR studies by purchasing compounds that are structurally related to the original hit.

For a broad outline of the steps and division of labor between SMDC personnel and user labs during this process, please see the Data Analysis and Cherry Pick section of the HTS Screening Workflow Outline ocated in the documents section.