7ZFX
VDR complex with Aromatic-D-Ring Analog
Summary for 7ZFX
| Entry DOI | 10.2210/pdb7zfx/pdb |
| Descriptor | Vitamin D3 receptor A, Nuclear receptor coactivator 1, ACETATE ION, ... (5 entities in total) |
| Functional Keywords | complex, agonist, vitamin d receptor, transcription |
| Biological source | Danio rerio (zebrafish) More |
| Total number of polymer chains | 2 |
| Total formula weight | 36394.53 |
| Authors | Rochel, N. (deposition date: 2022-04-01, release date: 2022-11-23, Last modification date: 2024-01-31) |
| Primary citation | Seoane, S.,Gogoi, P.,Zarate-Ruiz, A.,Peluso-Iltis, C.,Peters, S.,Guiberteau, T.,Maestro, M.A.,Perez-Fernandez, R.,Rochel, N.,Mourino, A. Design, Synthesis, Biological Activity, and Structural Analysis of Novel Des-C-Ring and Aromatic-D-Ring Analogues of 1 alpha ,25-Dihydroxyvitamin D 3. J.Med.Chem., 65:13112-13124, 2022 Cited by PubMed Abstract: The toxic calcemic effects of the natural hormone 1α,25-dihydroxyvitamin D (1,25D, 1,25-dihydroxycholecalciferol) in the treatment of hyperproliferative diseases demand the development of highly active and noncalcemic vitamin D analogues. We report the development of two highly active and noncalcemic analogues of 1,25D that lack the C-ring and possess an -phenylene ring that replaces the natural D-ring. The new analogues (, ) are characterized by an additional six-carbon hydroxylated side chain attached either to the aromatic nucleus or to the triene system. Both compounds were synthesized by the Pd-catalyzed tandem cyclization/cross coupling approach starting from alkyne and diphenol . Key steps include a stereoselective Cu-assisted addition of a Grignard reagent to an aromatic alkyne and a Takai olefination of an aromatic aldehyde. The new compounds are noncalcemic and show transcriptional and antiproliferative activities similar to 1,25D. Structural analysis revealed that they induce a large conformational rearrangement of the vitamin D receptor around helix 6. PubMed: 36166643DOI: 10.1021/acs.jmedchem.2c00900 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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