Novel retinoid X receptor (RXR) antagonists having a dicarba-closo-dodecaborane as a hydrophobic moiety.
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.
Ohta
Kiminori
K
Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Iijima
Toru
T
Kawachi
Emiko
E
Kagechika
Hiroyuki
H
Endo
Yasuyuki
Y
D001896:Boron Compounds / Q000737:chemistry* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047488:Retinoid X Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001896:Boron Compounds; D047488:Retinoid X Receptors; C100070:decaborane