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Designing of novel ERRγ inverse agonists by molecular modeling studies of docking and 3D-QSAR on hydroxytamoxifen derivatives
- Source :
- Medicinal Chemistry Research. 28:1661-1673
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- 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.
- Subjects :
- Agonist
Quantitative structure–activity relationship
Molecular model
010405 organic chemistry
Chemistry
medicine.drug_class
Organic Chemistry
Pharmacology toxicology
01 natural sciences
Combinatorial chemistry
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Docking (molecular)
medicine
Inverse agonist
General Pharmacology, Toxicology and Pharmaceutics
Subjects
Details
- ISSN :
- 15548120 and 10542523
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Medicinal Chemistry Research
- Accession number :
- edsair.doi...........dd9ae980b40cf1809b26a961f97f70b9