Abstract
Aim: Large numbers of biologically active compounds are available from which scaffolds (core structures) can be isolated and compared focusing on structural, potency and promiscuity criteria. Results: A computational analysis has been carried out to characterize all scaffolds and cyclic skeletons contained in currently available compounds from medicinal chemistry sources. Compounds active against hundreds of pharmaceutical targets were found to contain many structurally distinct scaffolds and cyclic skeletons. For given targets, these scaffolds often represent highly potent compounds. Conclusion: There is an abundance of scaffold diversity among specifically active compounds indicating that many pharmaceutically relevant proteins are highly permissive small molecular targets. These findings have several implications for drug discovery and design.
Acknowledgement
We thank the OpenEye [Citation25] Free Academic Licensing Program for providing a free academic license for the chemistry toolkit that was used to aid in the generation of data mining routines.
Financial & competing interests disclosure
D Stumpfe is supported by Sonderforschungsbereich 704 of the Deutsche Forschungsgemeinschaft. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.