The choice of which chemical libraries to screen should be guided by the goals of the project and the biological system of interest.
Biochemical screens seeking novel chemical entities capable of binding to a protein and modulating its function would be best served by diverse collections of drug-like small molecules such as the Maybridge HitFinder or the Chembridge MicroFormats. Confirmation and optimization of hits and can be managed by enlisting advice, collaborations, or through further contract work with the HTSC.
Cellular assays can reveal insights into the biological regulation of your phenotype with “known actives” and “approved drugs” collections. Screening characterized collections serves as a set of baseline controls to help hone the assay system and avoid false positives resulting from undesired biological effects. For example, one may wish to develop counter-screens to weed out cytotoxic compounds from consideration in a neuroscience screen. Many of the compounds in these collections have been validated in animals, allowing a progression to disease models by removing the hurdle of toxicology, pharmacokinetic, and pharmacodynamic studies.
If investigators would like to develop novel chemical compounds as hits with a long term view toward drug discovery, it is advisable to screen large and diverse collections of drug-like small molecules.
|NCI Diversity II||2,000||Diverse|
|Library||Size (# genes)||Redundancy|
|Human Kinases||646||2 oligos per gene|
|Human Phosphatases||222||2 oligos per gene|
|Human Druggable Genome||6,992||4 oligos per gene|
|Human Genome||21,687||3 oligos per gene|