6FO8

Vitamin D nuclear receptor complex 4

Summary for 6FO8

• Entry DOI: 10.2210/pdb6fo8/pdb
• Descriptor: Vitamin D3 receptor A, Nuclear receptor coactivator 1, (1~{R},3~{S},5~{Z})-4-methylidene-5-[(~{E})-3-[3-(6-methyl-6-oxidanyl-heptyl)phenyl]non-2-enylidene]cyclohexane-1,3-diol, ... (4 entities in total)
• Functional Keywords: nuclear receptor, ligand binding domain, transcription
• Biological source: Danio rerio (Zebrafish); More
• Total number of polymer chains: 2
• Total formula weight: 36147.30

Authors

Rochel, N. (deposition date: 2018-02-06, release date: 2018-05-16, Last modification date: 2024-01-17)

Primary citation

Gogoi, P.,Seoane, S.,Sigueiro, R.,Guiberteau, T.,Maestro, M.A.,Perez-Fernandez, R.,Rochel, N.,Mourino, A.
Aromatic-Based Design of Highly Active and Noncalcemic Vitamin D Receptor Agonists.
J. Med. Chem., 61:4928-4937, 2018

PubMed Abstract: We report the design, synthesis, biological evaluation, and structural analysis of a new class of vitamin D analogues that possess an aromatic m-phenylene D-ring and an alkyl chain replacing the C-ring. A key feature of the synthetic strategy is a stereoselective Pd-catalyzed construction of the triene system in aqueous medium that allows the rapid preparation of small amounts of VDR ligands for biological screening. Analogues with the shorter (2a) and longer (2d, 2e) side chains attached to the triene system have no calcemic activity. Compound 2a binds to VDR with the same order of magnitude than calcipotriol and oxacalcitriol. It also reduces proliferation in normal and tumor cells similarly to the natural hormone 1α,25-dihydroxyvitamin D, calcipotriol, and oxacalcitriol, suggesting preclinical studies related to hyperproliferative disorders such as psoriasis and cancer.

PubMed: 29733645
DOI: 10.1021/acs.jmedchem.8b00337

Experimental method

X-RAY DIFFRACTION (2.3 Å)