Novel Retinoid X Receptor Antagonists:  Specific Inhibition of Retinoid Synergism in RXR−RAR Heterodimer Actions

Abstract

Several 2-(arylamino)pyrimidine-5-carboxylic acids were designed as novel retinoid X receptor (RXR) antagonists. Compound 6a or 6b alone did not exhibit differentiation-inducing activity toward HL-60 cells and did not affect the activity of a retinoic acid receptor (RAR) agonist, Am80, but did inhibit the synergistic activity of an RXR agonist, PA024 (3), in the presence of Am80. The activity of 6 was ascribed to selective antagonism at the RXR site of RXR-RAR heterodimers.

Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells

“…To clarify the RA signaling pathway, we used RAR and RXR agonists. Am80 is an agonist for RARα and β [15], and PA024 is an RXR pan-agonist [16]. We demonstrated that these agonists weakly increased Ghrh-r gene expression (Fig.…”

Effect of retinoic acid on midkine gene expression in rat anterior pituitary cells

“…The cells (5 × 10 5 cells) were seeded in 24-well plates and then incubated at 37°C in a humidified atmosphere of 5% CO 2 and 95% air. The cells were then exposed to retinal (Sigma-Aldrich, St. Louis, MO, USA), all-trans retinoic acid (ATRA; Sigma-Aldrich), Am80 [11], or PA024 [12] at predetermined concentrations and durations. Am80 and PA024 were kindly provided by Dr. Hiroyuki Kagechika (School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan).…”

ApoC‐III gene expression is sharply increased during adipogenesis and is augmented by retinoid X receptor (RXR) agonists

“…3-Isobutyl-1-methylxanthine was from Wako. PA024 was previously described [14]. Taq-Man probes were from Applied Biosystems.…”