3AZ3

Crystal Structure Analysis of Vitamin D receptor

Summary for 3AZ3

• Entry DOI: 10.2210/pdb3az3/pdb
• Related: 3AZ1 3AZ2
• Descriptor: Vitamin D3 receptor, (4S)-4-hydroxy-5-[4-(3-{4-[(3S)-3-hydroxy-4,4-dimethylpentyl]-3-methylphenyl}pentan-3-yl)-2-methylphenoxy]pentanoic acid (3 entities in total)
• Functional Keywords: vitamin d receptor, hormone receptor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 1
• Total formula weight: 29244.95

Authors

Itoh, S.,Iijima, S. (deposition date: 2011-05-20, release date: 2011-11-02, Last modification date: 2024-03-13)

Primary citation

Kashiwagi, H.,Ono, Y.,Shimizu, K.,Haneishi, T.,Ito, S.,Iijima, S.,Kobayashi, T.,Ichikawa, F.,Harada, S.,Sato, H.,Sekiguchi, N.,Ishigai, M.,Takahashi, T.
Novel nonsecosteroidal vitamin D(3) carboxylic acid analogs for osteoporosis, and SAR analysis.
Bioorg.Med.Chem., 19:4721-4729, 2011

PubMed Abstract: Novel vitamin D(3) analogs with carboxylic acid were explored, focusing on a nonsecosteroidal analog, LG190178, with a bisphenyl skeleton. From X-ray analysis of these analogs with vitamin D receptor (VDR), the carboxyl groups had very unique hydrogen bonding interactions in VDR and mimicked 1α-hydroxy group and/or 3β-hydroxy group of 1α,25-dihydroxyvitamin D(3). A highly potent analog, 6a, with good in vitro activity and pharmacokinetic profiles was identified from an SAR study. Compound 6a showed significant prevention of bone loss in a rat osteoporosis model by oral administration.

PubMed: 21795053
DOI: 10.1016/j.bmc.2011.07.001

Experimental method

X-RAY DIFFRACTION (1.36 Å)