Compound collection screening

Lead Generation Based on Compound Collection Screening... 

A compound library is a compound collection. The compound libraries of large pharmaceutical and screening companies can exceed 1 million samples. Libraries are synthesized and stored as either individual samples or as combinations. 

Molecules in real solvents can exist in one or more tautomeric forms. The use of different tautomers in calculations can lead to significant variation in the estimated log P values (Pig. 15.1). Accurate prediction of the dominant tautomer requires ah initio calculahons. Due to speed limitations such calculations are not feasible for virtual screening and prediction of large compound collections. Moreover, the interpretation of the results can also be difficult, for example, the lacton-lactim (Pig. 15. IB) is the stable form of maleic hydrazide in the gas phase but the difference between this and the dilacton form (Pig. 15.1C and D) disappears in solution... 

Generally, performance of a method is often judged in one of two ways. The first is the enrichment factor, enrichment for short, which is the ratio of the cumulative number of actives in the top N% of the total number in the dataset to random retrieval rate. Many early studies focused on the enrichment obtained when the top 10% of the dataset was screened. However, this is operationally unrealistic if compound collections exceed 100,000 compounds, which is common in mid- to large-sized companies. A more realistic test is the enrichment obtained in the top... 

The potential sources of the compounds that are evaluated in a hit triage process are described in other chapters in this volume. These sources may include a high throughput screen (HTS) of a diverse compound collection, a targeted screen of... 

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