3WFG

Mineralocorticoid receptor ligand-binding domain with compuond 2e

Summary for 3WFG

• Entry DOI: 10.2210/pdb3wfg/pdb
• Related: 3VHU 3VHV 3WFF
• Descriptor: Mineralocorticoid receptor, 6-[(2S)-4-(4-fluorophenyl)-2-methyl-5-oxo-2,5-dihydrofuran-3-yl]-2H-1,4-benzoxazin-3(4H)-one, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: nuclear receptor, transcription factor, transcription, hypertension, non-steroidal antagonist, activating mutation, transcription-inhibitor complex, transcription/inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 32810.85

Authors

Sogabe, S.,Habuka, N. (deposition date: 2013-07-19, release date: 2013-08-21, Last modification date: 2023-11-08)

Primary citation

Hasui, T.,Ohra, T.,Ohyabu, N.,Asano, K.,Matsui, H.,Mizukami, A.,Habuka, N.,Sogabe, S.,Endo, S.,Siedem, C.S.,Tang, T.P.,Gauthier, C.,De Meese, L.A.,Boyd, S.A.,Fukumoto, S.
Design, synthesis, and structure-activity relationships of dihydrofuran-2-one and dihydropyrrol-2-one derivatives as novel benzoxazin-3-one-based mineralocorticoid receptor antagonists.
Bioorg.Med.Chem., 21:5983-5994, 2013

PubMed Abstract: Dihydrofuran-2-one and dihydropyrrol-2-one derivatives were identified as novel, potent and selective mineralocorticoid receptor (MR) antagonists by the structure-based drug design approach utilizing the crystal structure of MR/compound complex. Introduction of lipophilic substituents directed toward the unfilled spaces of the MR and identification of a new scaffold, dihydropyrrol-2-one ring, led to potent in vitro activity. Among the synthesized compounds, dihydropyrrol-2-one 11i showed an excellent in vitro activity (MR binding IC50=43nM) and high selectivity over closely related steroid receptors such as the androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) (>200-fold for AR and PR, 100-fold for GR).

PubMed: 23958516
DOI: 10.1016/j.bmc.2013.07.043

Experimental method

X-RAY DIFFRACTION (1.4 Å)