Promiscuity progression of bioactive compounds over time

Area of Science:

• Pharmacology
• Computational Chemistry
• Drug Discovery

Background:

• Compound promiscuity is defined as a small molecule's ability to interact with multiple biological targets.
• Understanding promiscuity progression is crucial for drug discovery and polypharmacology.
• Historical activity data provides insights into how compound promiscuity evolves over time.

Purpose of the Study:

• To analyze the progression and magnitude of compound promiscuity over nearly 40 years.
• To investigate the relationship between data growth and changes in compound promiscuity.
• To establish expectation values for promiscuity in bioactive compounds.

Main Methods:

• Analysis of nearly 1 million compounds and over 5.2 million activity records.
• Assembly of compound sets based on data confidence criteria and activity history.
• Temporal organization of data from 1976 to monitor growth and promiscuity progression.

Main Results:

• Consistently low degrees of compound promiscuity were detected across all analyzed sets.
• Promiscuity showed only small increases over time, with most compounds maintaining constant promiscuity.
• Even during periods of significant data growth, promiscuity levels remained stable or increased only slightly.
• High-confidence data indicates bioactive compounds interact with an average of 1.5 targets.

Conclusions:

• Bioactive compounds exhibit remarkably stable and low levels of promiscuity.
• Promiscuity progression is not significantly influenced by the massive growth of activity data.
• The findings provide valuable benchmarks for understanding compound promiscuity in drug discovery.