TEI-9647 

TEI-9647, a Vitamin D₃ Lactone analogue, is a potent and specific vitamin D receptor (VDR) antagonist. TEI-9647 inhibits VDR/VDRE-mediated genomic actions of 1α,25(OH)₂D₃. TEI-9647 inhibits bone resorption and HL-60 cell differentiation induced by of 1α,25(OH)₂D₃. TEI-9647 has the potential for suppressing the excessive bone resorption and osteoclast formation in Paget's disease^[1][2][3].

TEI-9647 (100 nM; 24 hours) treatment clearly suppresses p21^WAF1,CIP1 gene expression induced by 1α,25(OH)₂D₃^[1].
TEI-9647 (10-1000 nM; 96 hours) dose-dependently blocks the reciprocal changes of CD11b and CD71 expression associated with HL-60 cell differentiation induced by 1α,25(OH)₂D₃. TEI-9647 completely blocks the increase in CD11b and the decrease in CD71 expression at 100 nM^[1].
TEI-9647 blocks both 1α,25(OH)₂D₃-mediated HL-60 cell differentiation and also activation of the luciferase reporter in COS-7 cells that has been transfected with the cDNA containing the DRE of the rat 25(OH)D₃-24-hydroxylase gene and cDNA of the human vitamin D nuclear receptor^[1].
TEI-9647 can not induce cell differentiation even after treatment at 1 μM in HL-60 cell. TEI-9647 alone can not induce activation of NBT-reducing activity or α-NB esterase activity. In contrast, TEI-9647 markedly suppresses the up-regulation induced by 1α,25(OH)₂D₃ (0.1 nM) in HL-60 cells^[1].
TEI-9647 (0.001-1 μM; for 10 days) dose-dependently inhibits bone resorption induced by of 1α,25(OH)₂D₃ (1 nM). TEI-9647 alone never induces bone resorption even at 1 μM^[2].
TEI-9647 (10 nM; 12 h) markedly inhibits TAFII-17 and 25-OH-D₃-24-hydroxylase gene expression induced by 1α,25(OH)₂D₃ (0.1 nM) in bone marrow cells^[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

426.59

Solid

C₂₇H₃₈O₄

173388-20-0

O=C1O[C@@H](C[C@H]([C@H]2CC[C@@]3([H])/C(CCC[C@]23C)=C/C=C4C([C@@H](O)C[C@H](O)C\4)=C)C)CC1=C

Room temperature in continental US; may vary elsewhere.

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

• [1]. Miura D, et al. Antagonistic action of novel 1α,25-dihydroxyvitamin D₃-26, 23-lactone analogs on differentiation of human leukemia cells (HL-60) induced by 1α,25-dihydroxyvitamin D₃. J Biol Chem. 1999 Jun 4;274(23):16392-9.  [Content Brief]

  [2]. Seiichi Ishizuka, et al. Vitamin D antagonist, TEI-9647, inhibits osteoclast formation induced by 1α,25-dihydroxyvitamin D₃ from pagetic bone marrow cells. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):331-4.  [Content Brief]

  [3]. Kazuya Takenouchi, et al. Synthesis and structure-activity relationships of TEI-9647 derivatives as Vitamin D₃ antagonists. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):31-4.  [Content Brief]