TEI-9647 (100 nM; 24 hours) treatment clearly suppresses p21 WAF1,CIP1 gene expression induced by 1α,25(OH) 2 D 3 . 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) 2 D 3 . TEI-9647 completely blocks the increase in CD11b and the decrease in CD71 expression at 100 nM. TEI-9647 blocks both 1α,25(OH) 2 D 3 -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)D 3 -24-hydroxylase gene and cDNA of the human vitamin D nuclear receptor. 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) 2 D 3 (0.1 nM) in HL-60 cells. TEI-9647 (0.001-1 μM; for 10 days) dose-dependently inhibits bone resorption induced by of 1α,25(OH) 2 D 3 (1 nM). TEI-9647 alone never induces bone resorption even at 1 μM. TEI-9647 (10 nM; 12 h) markedly inhibits TAFII-17 and 25-OH-D 3 -24-hydroxylase gene expression induced by 1α,25(OH) 2 D 3 (0.1 nM) in bone marrow cells. RT-PCR Cell Line: HL-60 cells Concentration: 100 nM Incubation Time: 24 hours Result: Clearly suppressed p21 WAF1,CIP1 gene expression induced by 1α,25(OH) 2 D 3 .

TEI-9647 是一种 Vitamin D3 Lactone 类似物，是一种有效的，特异性的维生素 D 受体 (VDR) 拮抗剂。 TEI-9647 抑制 VDR/VDRE 介导的 1α,25(OH)2D3 的基因组作用。TEI-9647 可以抑制 1α,25(OH)2D3 诱导的骨吸收和 HL-60 细胞分化。TEI-9647 有潜力用于抑制 Paget 病中过度的骨吸收和破骨细胞形成。