9VOG

Vitamin D receptor complex with a 5-{4-(m-carboran-1-yl)phenoxy}-4-hydroxypentanoic acid derivative

This is a non-PDB format compatible entry.

Summary for 9VOG

• Entry DOI: 10.2210/pdb9vog/pdb
• Descriptor: Vitamin D3 receptor, Mediator of RNA polymerase II transcription subunit 1, (S)-5-[4-{7-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl)-1,7-dicarba-closo-dodecaboran-1-yl}phenoxy]-4-hydroxypentanoic acid, ... (4 entities in total)
• Functional Keywords: vitamin d receptor, transcription
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 2
• Total formula weight: 32760.49

Authors

Mudiyanselage, H.N.T.N.,Hanazono, Y.,Ito, N.,Kagechika, H.,Fujii, S. (deposition date: 2025-07-01, release date: 2025-12-03)

Primary citation

Mudiyanselage, H.N.T.N.,Misawa, T.,Ochiai, K.,Demizu, Y.,Hanazono, Y.,Ito, N.,Fujii, S.
Design, synthesis and structural development of nonsecosteroidal VDR ligands based on the C,C'-diphenyl-m-carborane scaffold.
Eur.J.Med.Chem., 302:118320-118320, 2025

PubMed Abstract: Nonsecosteroidal vitamin D receptor (VDR) ligands are promising drug candidates for multiple diseases, including osteoporosis, psoriasis, and certain cancers. We report here the design, synthesis, biological evaluation and crystallographic analysis of a series of 1,7-diphenyl-m-carborane derivatives as novel nonsecosteroidal VDR ligands. We found that the 1,7-diphenyl-m-carborane framework is a promising hydrophobic core of VDR ligands, and developed a series of potent compounds such as 12b and 13a. Interestingly, compounds with different chain length exhibited similar potencies. X-Ray co-crystal structure analysis revealed that the developed compounds exhibited various different interaction patterns depending on the structure of the carboxyalkyl chain, indicating that the ligand-binding pocket of the VDR possesses sufficient conformational plasticity to accommodate a wide variety of ligands without compromising activity. The developed carborane derivatives are promising leads for further structural development, and the findings on the diversity of binding modes will be helpful in the design of other VDR ligands.

PubMed: 41205515
DOI: 10.1016/j.ejmech.2025.118320

Experimental method

X-RAY DIFFRACTION (1.43 Å)