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How promiscuous are pharmaceutically relevant compounds? A data-driven assessment.

ABSTRACT: Given the increasing notion of target promiscuity of bioactive compounds and polypharmacological drug behavior, a detailed analysis of publicly available compound activity data from medicinal chemistry sources was carried out to determine and quantify the degree of promiscuity of active compounds across all known human target families. The results are surprising. Approximately 62% of currently available compounds with high-confidence activity data are only annotated with a single biological target, whereas 36% are known to act against multiple targets within the same family (i.e., closely related targets). However, only ~2% of bioactive compounds are promiscuous across different target families. Thus, despite general data sparseness, these findings indicate that highly promiscuous bioactive compounds only rarely occur. Because pharmaceutically relevant active compounds represent the pool from which drug candidates emerge, one might extrapolate from these results and conclude that there is a low statistical probability to obtain drugs that act against multiple targets belonging to distinct families.

SUBMITTER: Hu Y

PROVIDER: S-EPMC3535109 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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How promiscuous are pharmaceutically relevant compounds? A data-driven assessment.

Hu Ye Y Bajorath Jürgen J

The AAPS journal 20121023 1

Given the increasing notion of target promiscuity of bioactive compounds and polypharmacological drug behavior, a detailed analysis of publicly available compound activity data from medicinal chemistry sources was carried out to determine and quantify the degree of promiscuity of active compounds across all known human target families. The results are surprising. Approximately 62% of currently available compounds with high-confidence activity data are only annotated with a single biological targ ...[more]

PMID: 23090085

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How promiscuous are pharmaceutically relevant compounds? A data-driven assessment.

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How promiscuous are pharmaceutically relevant compounds? A data-driven assessment.

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