8PWD
Crystal structure of VDR in complex Des-C-Ring and Aromatic-D-Ring analog 3c
Summary for 8PWD
| Entry DOI | 10.2210/pdb8pwd/pdb |
| Descriptor | Vitamin D3 receptor A, Nuclear receptor coactivator 2, (1R,3S,5Z)-4-methylidene-5-[(E)-3-[3-[7,7,7-tris(fluoranyl)-6-oxidanyl-6-(trifluoromethyl)hept-3-ynyl]phenyl]pent-2-enylidene]cyclohexane-1,3-diol, ... (4 entities in total) |
| Functional Keywords | nuclear receptor, vdr, agonist, transcription |
| Biological source | Danio rerio (zebrafish) More |
| Total number of polymer chains | 2 |
| Total formula weight | 36143.03 |
| Authors | Rochel, N. (deposition date: 2023-07-20, release date: 2024-08-14, Last modification date: 2025-03-12) |
| Primary citation | Zarate-Ruiz, A.,Seoane, S.,Peluso-Iltis, C.,Peters, S.,Gregorio, C.,Guiberteau, T.,Maestro, M.,Perez-Fernandez, R.,Rochel, N.,Mourino, A. Further Studies on the Highly Active Des-C-Ring and Aromatic-D-Ring Analogues of 1 alpha ,25-Dihydroxyvitamin D 3 (Calcitriol): Refinement of the Side Chain. J.Med.Chem., 66:15326-15339, 2023 Cited by PubMed Abstract: Current efforts in the vitamin D field are directed toward the development of highly antiproliferative yet noncalcemic analogues of the natural hormone 1α,25-dihydroxyvitamin D (1,25D). We have recently reported the design, synthesis, biological evaluation, and crystal structures of a series of novel analogues that both lack the steroidal C-ring and have an -phenylene ring replacing the steroidal cyclopentane D-ring. We have now investigated the potentiating effects of incorporating selected modifications (hexafluorination and/or an internal triple bond) within the steroidal side chain in our series. An alternative synthetic strategy (Wittig-Horner approach instead of our previously used Pd-catalyzed tandem cyclization/cross-coupling) for the construction of the vitamin D triene system was found convenient for the target compounds , , , and of this report. These modifications enhance vitamin D nuclear receptor (VDR) interactions and consequently VDR-associated biological properties compared to parental PG-136 compound while maintaining normal calcium levels. PubMed: 37910811DOI: 10.1021/acs.jmedchem.3c01371 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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