Ohta Kiminori, Iijima Toru, Kawachi Emiko, Kagechika Hiroyuki, Endo Yasuyuki
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5913-8. doi: 10.1016/j.bmcl.2004.09.035.
We designed and synthesized novel retinoid X receptor (RXR)-selective antagonists bearing a carborane moiety. Compounds 8a-d or 9a-d themselves have no differentiation-inducing activity toward HL-60 cells and no inhibitory activity towards a retinoic acid receptor (RAR) agonist. However, they inhibit the synergistic activity of an RXR agonist, PA024, in the presence of Am80 on the cell differentiation of HL-60. Transactivation assay using RARs and RXRs suggested that the inhibitory activity of 9b resulted from the selective antagonism at the RXR site of RXR-RAR heterodimers.
我们设计并合成了带有碳硼烷部分的新型类视黄醇X受体（RXR）选择性拮抗剂。化合物8a-d或9a-d本身对HL-60细胞没有诱导分化活性，对维甲酸受体（RAR）激动剂也没有抑制活性。然而，在存在Am80的情况下，它们抑制了RXR激动剂PA024对HL-60细胞分化的协同活性。使用RAR和RXR的反式激活分析表明，9b的抑制活性源于对RXR-RAR异二聚体RXR位点的选择性拮抗作用。
