Vitamin D receptor (VDR) is a member of the nuclear receptor family of transcription factors. Calcitriol (the active form of vitamin D, 1,25-(OH)2 vitamin D3) binds to VDR and then forms a heterodimer with retinol X receptor. Besides, VDR binding leads to the expression or reverse transcription of many specific gene products. Specifically, VDR is also involved in microRNA-directed post-transcriptional mechanism. VDR is expressed in most human tissues and regulates the transcription of genes related to intestinal and renal transport of calcium and other minerals.

Moreover, VDR gene encodes the nuclear hormone receptor of vitamin D. The most effective natural agonist is calcitriol (1,25-dihydroxycholecalciferol), and vitamin D2 homocalcitriol (1-α, 25-dihydroergocalcidol) is also a strong activator. Furthermore, the receptor regulates a variety of other metabolic pathways, such as those associated with immune response and cancer. The basic biological activity of vitamin D3, 1a, 25-dihydroxy vitamin-min D3 (1a, 25(OH)2D3) is to promote intestinal calcium absorption and increase bone calcium mobilization. Today, we will introduce a specific vitamin D receptor (VDR) antagonist, TEI-9648.

TEI-9648 is a Specific Vitamin D Receptor (VDR) Antagonist.

First of all, TEI-9648, a Vitamin D3 Lactone analog, is a potent and specific vitamin D receptor (VDR) antagonist. Meanwhile, TEI-9648 inhibits VDR/VDRE-mediated genomic actions of 1α,25(OH)2D3. Nonetheless, TEI-9648 also inhibits HL-60 cell differentiation induced by of 1α,25(OH)2D3. TEI-9648 has the potential for bone metabolism research.

In the second place, TEI-9648 with 10-1000 nM dose-dependently blocks the reciprocal changes of CD11b and CD71 expression associated with HL-60 cell differentiation induced by 1α,25(OH)2D3. Particularly, TEI-9648 has a consistently weaker suppressive effect than TEI-9647. Obviously, TEI-9648 can not induce cell differentiation even after treatment at 1 μM in HL-60 cells.

Last but not the least, TEI-9648 alone can not induce activation of NBT-reducing activity or α-NB esterase activity. In contrast, TEI-9648 markedly suppresses the up-regulation induced by 1α,25(OH)2D3 (0.1 nM) in HL-60 cells.

All in all, TEI-9648 is a potent and specific vitamin D receptor (VDR) antagonist.


Miura D, et al. J Biol Chem. 1999 Jun 4;274(23):16392-9.