TEI-9647 is a vitamin D3 lactone analog that specifically inhibits vitamin D receptor activity[1-2]. TEI-9647 has anti-inflammatory effects and has also been used in research exploring the treatment of Paget's disease[3-4].
In vitro, when human promyelocytic leukemia cells (HL-60) were pretreated with TEI-9647 (1nM–1μM) for 24–96 hours, TEI-9647 significantly inhibited HL-60 cell differentiation[5].
In vivo, a single intravenous co-administration of TEI-9647 (2–50μg/kg) with 1α,25(OH)₂D₃ (0.25μg/kg) to vitamin D-deficient rats significantly suppressed the genomic effects of 1α,25(OH)₂D₃ on intestinal calcium transport and bone calcium mobilization 24 hours after treatment[6].
References:
[1] Takenouchi K, Sogawa R, Manabe K, 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.
[2] Miura D, Manabe K, Ozono K, et al. Antagonistic action of novel 1alpha,25-dihydroxyvitamin D3-26, 23-lactone analogs on differentiation of human leukemia cells (HL-60) induced by 1alpha,25-dihydroxyvitamin D3. J Biol Chem. 1999 Jun 4;274(23):16392-9.
[3] Dixon KM, Deo SS, Wong G, et al. Skin cancer prevention: a possible role of 1,25dihydroxyvitamin D3 and its analogs. J Steroid Biochem Mol Biol. 2005 Oct;97(1-2):137-43.
[4] Díaz L, Noyola-Martínez N, Barrera D, et al. Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts. J Reprod Immunol. 2009 Jul;81(1):17-24.
[5] Ishizuka S, Kurihara N, Hiruma Y, et al. 1alpha,25-Dihydroxyvitamin D(3)-26,23-lactam analogues function as vitamin D receptor antagonists in human and rodent cells. J Steroid Biochem Mol Biol. 2008 Jun;110(3-5):269-77.
[6] Ishizuka S, Miura D, Ozono K, et al. Antagonistic Actions in Vivo of (23S)-25-Dehydro-1alpha-Hydroxyvitamin D(3-)26,23-Lactone on Calcium Metabolism Induced by 1alpha,25-Dihydroxyvitamin D(3). Endocrinology. 2001 Jan;142(1):59-67.
TEI-9647是一种维生素D3内酯类似物，可特异性抑制维生素D受体活性[1-2]。TEI-9647具有抑制炎症反应的功能，还被用于探索治疗佩吉特病的研究中[3-4]。
在体外，TEI-9647（1nM-1μM）预处理人早幼粒白血病细胞（HL-60）24-96小时，TEI-9647显著抑制HL-60细胞分化[5]。
在体内，TEI-9647（2–50μg/kg）与1α,25(OH)₂D₃（0.25μg/kg）联合静脉单次注射至维生素D缺乏大鼠体内，24小时后显著抑制由1α,25(OH)₂D₃介导的肠道钙转运和骨钙动员的基因组效应[6]。