Journal
AAPS JOURNAL
Volume 15, Issue 3, Pages 808-815Publisher
SPRINGER
DOI: 10.1208/s12248-013-9488-0
Keywords
active compounds; activity measurements; compound promiscuity; confirmatory assays; polypharmacology; screening data; targets
Categories
Ask authors/readers for more resources
Compound promiscuity refers to the ability of small molecules to specifically interact with multiple targets, which represents the origin of polypharmacology. Promiscuity is thought to be a widespread characteristic of pharmaceutically relevant compounds. Yet, the degree of promiscuity among active compounds from different sources remains uncertain. Here, we report a thorough analysis of compound promiscuity on the basis of more than 1,000 PubChem confirmatory bioassays, which yields an upper-limit assessment of promiscuity among active compounds. Because most PubChem compounds have been tested in large numbers of assays, data sparseness has not been a limiting factor for the current analysis. We have determined that there is an overall likelihood of similar to 50% of an active PubChem compound to interact with two or more targets. The probability to interact with more than five targets is reduced to 7.6%. On average, an active PubChem compound was found to interact with similar to 2.5 targets. Moreover, if only activities consistently detected in all assays available for a given target were considered, this ratio was further reduced to similar to 2.3 targets per compound. For comparison, we have also analyzed high-confidence activity data from ChEMBL, the major public repository of compounds from medicinal chemistry, and determined that an active ChEMBL compound interacted on average with only similar to 1.5 targets. Taken together, our results indicate that the degree of compound promiscuity is lower than often assumed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available