Gene/Protein
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Pivot Concepts:
Gene/Protein
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Target Concepts:
Gene/Protein
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Query: EC:6.2.1.1 (
ACS
)
78,556
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nuclear receptor coregulators are master regulators of transcription and selectively interact with the vitamin D receptor (VDR) to modulate cell differentiation, cell proliferation and calcium homeostasis. Herein, we report the syntheses and evaluation of highly potent and selective VDR-coactivator inhibitors based on a recently identified 3-indolylmethanamine scaffold. The most active compound, PS121912, selectively inhibited VDR-mediated transcription among eight other nuclear receptors tested. PS121912 is also selectively disrupting the binding between VDR and the third nuclear receptor interaction domain of the coactivator
SRC2
. Genetic studies revealed that PS121912 behaves like a VDR antagonist by repressing 1,25-(OH)
2
D
3
activated gene transcription. In addition, PS121912 induced apoptosis in HL-60.
ACS
Med Chem Lett 2014 Feb 13
PMID:Development of novel Vitamin D Receptor-Coactivator Inhibitors. 2479 95
