Promiscuous compound

It can however be used in a standardized profiling panel calibrated against known promiscuous compounds. The THR classification given above is used in the Novartis in vitro safety pharmacology profiling panel where >50 targets have been tested. 

To check the chemical diversity of the dataset, compounds tvere clustered in 843 singletons and 1836 chemical classes containing at least tv ro molecules. The biggest cluster had 72 members. The singleton set contains only 10% of promiscuous compounds. Classes tvith more than 20 compounds contain a higher number of promiscuous compounds. In fact, classes tvith 20-30 members have 25% promiscuous members and classes with >30 members have 40% promiscuous members. 

Promiscuous features are to be avoided, whereas selective features can be used to change promiscuous compounds. Such information needs to be fed back into projects that submit compounds for safety profiling. A sample result from Azzaoui s analysis is shown in Table 1. 

Researchers from BMS have detailed the results of their efforts to enhance their HTS process [34]. Their papers discuss the subjectivity of the typical chemical structure triage process as it relates to HTS analysis, a topic worth some investigation by anyone involved in this type of selection process. With the aim of reducing subjectivity in this area, the authors systematically review their filters for physicochemical properties (this topic discussed in more detail below) and unwanted chemical moieties. Much of the work is aimed at understanding and detecting promiscuous compounds - those that initially appear to be hits in many screens (this topic discussed in more detail below). Importantly, the authors have made some of the related tools available for public use. 

To avoid confusion, here we use the term pharmacologically promiscuous compound to refer to compounds that are truly active on several drug targets and the term screening artifact to describe compounds that are active in an assay for any reason other than specific activity toward the protein target of interest. 

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