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]. In Vitro: 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].