HX 531 is a potent retinoid X receptor (RXR) antagonist[1].
In vitro, Pre-treatment with HX 531 (2.5μM; 30min) attenuated the anti-apoptotic effect of all-trans retinoic acid (t-RA) in protecting mesangial cells from H₂O₂-induced apoptosis via the inhibition of the activator protein 1 (AP-1) pathway[2]. HX 531 (0.1μM; 45-60min) significantly inhibits Benzophenone-3 (BP-3)-induced neuronal apoptosis and partially reverses the effects of BP-3 on the expression of RXR receptors and epigenetic status[3].
In vivo, Wild-type mice treated with HX 531(2 weeks; p.o.) were protected from high-fat (HF) diet-induced hyperglycemia and insulin resistance[4]. The weight gain of OLETF rats treated with HX 531 (10mg/kg/day; 22 weeks; p.o.) was significantly suppressed, and the fat pad weight was significantly reduced, comparable to that of non-diabetic LETO rats[5].
References:
[1] Alique M, Lucio FJ, Herrero JF. Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration. Br J Pharmacol. 2006 Sep;149(1):65-72.
[2] Konta T, Xu Q, Furusu A, et al. Selective roles of retinoic acid receptor and retinoid x receptor in the suppression of apoptosis by all-trans-retinoic acid. J Biol Chem. 2001 Apr 20;276(16):12697-701.
[3] Wnuk A, Rzemieniec J, Lasoń W, et al. Benzophenone-3 Impairs Autophagy, Alters Epigenetic Status, and Disrupts Retinoid X Receptor Signaling in Apoptotic Neuronal Cells. Mol Neurobiol. 2018 Jun;55(6):5059-5074.
[4] Yamauchi T, Waki H, Kamon J, et al. Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes. J Clin Invest. 2001 Oct;108(7):1001-13.
[5] Nakatsuka A, Wada J, Hida K, et al. RXR antagonism induces G0 /G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes. J Pathol. 2012 Apr;226(5):784-95.
HX 531是一种强效的视黄醇X受体（RXR）拮抗剂[1]。
在体外实验中，用HX 531（2.5μM; 30分钟）预处理可减弱全反式维甲酸（t-RA）通过抑制激活蛋白1（AP-1）通路保护系膜细胞免受H₂O₂诱导的凋亡的抗凋亡作用[2]。HX 531（0.1μM; 45-60分钟）显著抑制苯甲酮-3（BP-3）诱导的神经元凋亡，并部分逆转BP-3对RXR受体表达和表观遗传状态的影响[3]。
在体内实验中，野生型小鼠经HX 531（2周; 口服）处理后，可免受高脂（HF）饮食诱导的高血糖和胰岛素抵抗[4]。用HX 531（10mg/kg/天; 22周; 口服）处理的OLETF大鼠体重增长显著受到抑制，脂肪垫重量显著减少，与非糖尿病LETO大鼠相当[5]。