Abstract
Suppression of vitamin D receptor (VDR)-mediated transcription is expected to be of therapeutic value in Paget's disease of bone. It is known that interaction between VDR and coactivators is necessary for VDR transactivation, and the interaction occurs when VDR recognizes an LXXLL peptide motif of coactivators. We previously reported that benzodiazepine derivatives designed as LXXLL peptide mimetics inhibited the interaction of VDR and coactivators, and reduced VDR transcription. Here, we investigated the structure-activity relationship of 7- and 8-substituted benzodiazepine derivatives, and established that the amino group at the 8-position is critical for the inhibitory activity.
Original language | English |
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Pages (from-to) | 993-1005 |
Number of pages | 13 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 21 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2013 Feb 15 |
Externally published | Yes |
Keywords
- Antagonist
- Cofactor
- LXXLL
- Non-peptide
- Nuclear receptor
- Protein interaction inhibitor
- Structure-activity relationship
- Vitamin D
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry