Exploring Structural Relationships between Bioactive and Commercial Chemical Space and Developing Target Hypotheses for Compound Acquisition

ACS Omega
Carmen CerchiaJürgen Bajorath

Abstract

Analog series were systematically extracted from more than 650 000 bioactive compounds originating from medicinal chemistry and screening sources and more than 3.6 million commercial compounds that were not biologically annotated. Then, analog series-based (ASB) scaffolds were generated. For each scaffold from a bioactive series, a target profile was derived and ASB scaffolds shared by bioactive and commercial compounds were determined. On the basis of our analysis, large segments of commercial chemical space were not yet explored biologically. Shared ASB scaffolds established structural relationships between bioactive and commercial chemical space, and the target profiles of these scaffolds were transferred to commercially available analogs of active compounds. This made it possible to derive target hypotheses for more than 37 000 compounds without biological annotations covering more than 1000 different targets. For many molecules, alternative target assignments were available. Target hypotheses for these compounds should be of interest, for example, for hit expansion, acquisition of compounds to design or further extend focused libraries for drug discovery, or testing of expanded analog series on different targets. They can ...Continue Reading

References

Feb 4, 2010·Journal of Chemical Information and Modeling·Jameed Hussain, Ceara Rea
Sep 29, 2011·Nucleic Acids Research·Anna GaultonJohn P Overington
Dec 6, 2011·Nucleic Acids Research·Yanli WangStephen H Bryant
Apr 12, 2012·Journal of Chemical Information and Modeling·Xiaoying HuJürgen Bajorath
Oct 29, 2014·Nucleic Acids Research·UNKNOWN UniProt Consortium
Oct 20, 2015·Journal of Chemical Information and Modeling·Teague Sterling, John J Irwin
Feb 4, 2016·Journal of Medicinal Chemistry·Ye HuJürgen Bajorath
Apr 16, 2016·PloS One·Swarit JasialJürgen Bajorath

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Citations

Apr 29, 2021·Open Biology·Fatemeh AliabadiThomas J Webster
Jul 29, 2021·Journal of Cheminformatics·Candida ManelfiAndrea Rosario Beccari

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Software Mentioned

KNIME
ChEMBL
Perl
OpenEye
ZINC
PubChem BioAssays
PubChem
Python scripts

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