Identifying new liver X receptor alpha modulators and distinguishing between agonists and antagonists by crystal ligand pocket screening
| Autor: | Ying-Ting Lin, Wen-Hao Yu, Yi-Jing Chuang, Chien-Fu Huang, Jia-Hau Lee, Chin-Chung Wu, Chang-Yin Lee |
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| Rok vydání: | 2020 |
| Předmět: |
Agonist
medicine.drug_class Binding pocket Computational biology Crystallography X-Ray Ligands 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Humans Organic Chemicals Liver X Receptors 030304 developmental biology Pharmacology 0303 health sciences Reporter gene Virtual screening Binding Sites Chemistry Liver X receptor alpha In vitro Molecular Docking Simulation Docking (molecular) 030220 oncology & carcinogenesis Molecular Medicine |
| Zdroj: | Future Medicinal Chemistry. 12:1227-1237 |
| ISSN: | 1756-8927 1756-8919 |
| DOI: | 10.4155/fmc-2020-0069 |
| Popis: | Background: Modulators of LXRα are of high pharmacological interest as LXRα regulates fatty acid metabolism, inflammatory processes and cancer. We aim to identify new LXRα modulators and to recognize a distinguishable feature of agonists. Results&methodology: The ligand self-dock and largest-cavity-size searching purposely located two appropriate ligand-binding sites to reach the two aims. One is identifying the new modulators from Maybridge library. 20 new compounds are confirmed by the in vitro reporter gene assay. The other is denoting an agonist by at least one best docking pose having one hydrogen bond to LXRα Helix12 His421. Conclusion: Based on the quality x-ray binding pocket, we can identify new LXRα modulators and distinguish between agonists and antagonists by molecular docking. |
| Databáze: | OpenAIRE |
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