3P8X

Synthesis, Structure, and Biological Activity of des-Side Chain Analogues of 1alpha,25-Dihydroxyvitamin D3 with Substituents at C-18

Summary for 3P8X

• Entry DOI: 10.2210/pdb3p8x/pdb
• Related: 1DB1
• Descriptor: Vitamin D3 receptor, (1R,3S,5Z)-5-{(2E)-2-[(3aR,7aS)-7a-(7-hydroxy-7-methyloctyl)octahydro-4H-inden-4-ylidene]ethylidene}-4-methylidenecyclohexane-1,3-diol, SULFATE ION, ... (4 entities in total)
• Functional Keywords: helices sandwich, transcription regulation, vitamin d, transcription regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 1
• Total formula weight: 32303.18

Authors

Rochel, N.,Sato, Y.,Moras, D. (deposition date: 2010-10-15, release date: 2011-08-31, Last modification date: 2024-02-21)

Primary citation

Verlinden, L.,Verstuyf, A.,Eelen, G.,Bouillon, R.,Ordonez-Moran, P.,Larriba, M.J.,Munoz, A.,Rochel, N.,Sato, Y.,Moras, D.,Maestro, M.,Seoane, S.,Dominguez, F.,Eduardo-Canosa, S.,Nicoletti, D.,Moman, E.,Mourino, A.
Synthesis, Structure, and Biological Activity of des-Side Chain Analogues of 1 ,25-Dihydroxyvitamin D3 with Substituents at C-18
Chemmedchem, 6:788-793, 2011

PubMed Abstract: An improved synthetic route to 1α,25-dihydroxyvitamin D(3) des-side chain analogues 2 a and 2 b with substituents at C18 is reported, along with their biological activity. These analogues display significant antiproliferative effects toward MCF-7 breast cancer cells and prodifferentiation activity toward SW480-ADH colon cancer cells; they are also characterized by a greatly decreased calcemic profile. The crystal structure of the human vitamin D receptor (hVDR) complexed to one of these analogues, 20(17→18)-abeo-1α,25-dihydroxy-22-homo-21-norvitamin D(3) (2 a) reveals that the side chain introduced at position C18 adopts the same orientation in the ligand binding pocket as the side chain of 1α,25-dihydroxyvitamin D(3).

PubMed: 21520419
DOI: 10.1002/cmdc.201100021

Experimental method

X-RAY DIFFRACTION (1.7 Å)