5AVI
Crystal structure of LXRalpha in complex with tert-butyl benzoate analog, compound 4
Summary for 5AVI
| Entry DOI | 10.2210/pdb5avi/pdb |
| Descriptor | Oxysterols receptor LXR-alpha, Nuclear receptor coactivator 1, tert-butyl 2-[[4-[ethanoyl(methyl)amino]phenoxy]methyl]-5-(trifluoromethyl)benzoate, ... (4 entities in total) |
| Functional Keywords | agonist, complex, transcription |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Nucleus : Q13133 Q15788 |
| Total number of polymer chains | 4 |
| Total formula weight | 72191.96 |
| Authors | Matsui, Y.,Hanzawa, H.,Tamaki, K. (deposition date: 2015-06-16, release date: 2015-08-26, Last modification date: 2023-11-08) |
| Primary citation | Matsui, Y.,Yamaguchi, T.,Yamazaki, T.,Yoshida, M.,Arai, M.,Terasaka, N.,Honzumi, S.,Wakabayashi, K.,Hayashi, S.,Nakai, D.,Hanzawa, H.,Tamaki, K. Discovery and structure-guided optimization of tert-butyl 6-(phenoxymethyl)-3-(trifluoromethyl)benzoates as liver X receptor agonists Bioorg.Med.Chem.Lett., 25:3914-3920, 2015 Cited by PubMed Abstract: To obtain potent liver X receptor (LXR) agonists, a structure-activity relationship study was performed on a series of tert-butyl benzoate analogs. As the crystal structure analysis suggested applicable interactions between the LXR ligand-binding domain and the ligands, two key functional groups were introduced. The introduction of the hydroxyl group on the C6-position of the benzoate part enhanced the agonistic activity in a cell-based assay, and the carboxyl group in terminal improved the pharmacokinetic profile in mice, respectively. The obtained compound 32b increased blood ABCA1 mRNA expression without plasma TG elevation in both mice and cynomolgus monkeys. PubMed: 26238323DOI: 10.1016/J.BMCL.2015.07.047 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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