Designing of novel ERRγ inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives
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ERRγinverse agonist is a powerful therapeutic target for the treatment of cancers and certain metabolic disorders. Until now, only GSK5814 was reported as selective ERRγinverse agonist. So 60 newly hydroxytamoxifen analogues were selected to perform molecular docking and 3D-QSAR study to design more selective inverse agonist of ERRγ. Both established CoMFA and CoMSIA models obtained high predictive and satisfactory value, demonstrated that bulky, hydrophobic and negative electrostatic substitutions are preferred at R2 position, and introducing hydrophilic and H-bond donor and acceptor groups at R1 and R4 positions is greatly important for improving binding activities. The obtained information will be useful to provide clues for rationally designing novel and high potency ERRγinverse agonists.
KeywordsERRγinverse agonist Molecular docking 3D-QSAR CoMFA CoMSIA
This work were supported by a grant from the National Natural Science Foundation of China (81872744) and Shandong Natural Science Foundation of China (ZR2019MH046).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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