T0901317 is an orally active and highly selective LXR agonist with EC50=15nM for LXRα, and activates xenobiotic receptor pregnane X receptor (PXR) with EC50=23nM[1]. T0901317 has been used to regulate liver function and fat metabolism in different models[2].
In vitro, T0901317 treatment at 5μM for 24 hours significantly inhibited the migration and invasion of A549 cells[3]. Treatment with 10µM T0901317 for 30min completely suppressed the fluctuation of cytosolic Ca2+ concentration induced by 15mM glucose and suppressed mitochondrial metabolism in mouse β cells [4]. Treatment of CaOV3 cells with 10μM T0901317 for 24 hours significantly inhibited cell proliferation, significantly increased caspase activity, and increased the number of apoptotic cells[5].
In vivo, T0901317 treatment (50mg/kg/day; p.o.) for 7 weeks alleviated cardiac hypertrophy and improved hemodynamic function after aortic constriction in mice [6]. Intraperitoneal administration of T0901317(50 mg/kg/day) to male db/db mice for 12 days resulted in hypertriglyceridemia and deepened hepatic triglyceride accumulation[7]. Treatment of 11-week-old APP23 mice with T0901317 (50 mg/kg/day) via gastric gavage for 6 days resulted in a significant increase in ABCA1 expression and a decrease in soluble amyloid precursor protein (APP)[8].
References:
[1] Mitro N, Vargas L, Romeo R, et al. T0901317 is a potent PXR ligand: implications for the biology ascribed to LXR[J]. FEBS letters, 2007, 581(9): 1721-1726.
[2] Houck K A, Borchert K M, Hepler C D, et al. T0901317 is a dual LXR/FXR agonist[J]. Molecular genetics and metabolism, 2004, 83(1-2): 184-187.
[3] Lou R, Cao H, Dong S, et al. Liver X receptor agonist T0901317 inhibits the migration and invasion of non-small-cell lung cancer cells in vivo and in vitro[J]. Anti-cancer drugs, 2019, 30(5): 495-500.
[4] Maczewsky J, Sikimic J, Bauer C, et al. The LXR ligand T0901317 acutely inhibits insulin secretion by affecting mitochondrial metabolism[J]. Endocrinology, 2017, 158(7): 2145-2154.
[5] Rough J J, Monroy M A, Yerrum S, et al. Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells[J]. Journal of ovarian research, 2010, 3(1): 13.
[6] Kuipers I, Li J, Vreeswijk‐Baudoin I, et al. Activation of liver X receptors with T0901317 attenuates cardiac hypertrophy in vivo[J]. European journal of heart failure, 2010, 12(10): 1042-1050.
[7] Chisholm J W, Hong J, Mills S A, et al. The LXR ligand T0901317 induces severe lipogenesis in the db/db diabetic mouse[J]. Journal of lipid research, 2003, 44(11): 2039-2048.
[8] Koldamova R P, Lefterov I M, Staufenbiel M, et al. The liver X receptor ligand T0901317 decreases amyloid β production in vitro and in a mouse model of Alzheimer's disease[J]. Journal of Biological Chemistry, 2005, 280(6): 4079-4088.
T0901317是一种口服活性高选择性LXR激动剂，对LXRα的EC50为15nM，并能激活异生物质受体孕烷X受体(PXR)，EC50为23nM[1]。T0901317已被用于不同模型中调节肝功能及脂肪代谢[2]。
在体外，5μM浓度的T0901317处理24小时可显著抑制A549细胞的迁移和侵袭能力[3]。10µM 浓度的T0901317处理30min可完全抑制15mM葡萄糖诱导的小鼠β细胞胞浆Ca2+浓度波动，抑制线粒体代谢[4]。用10μM浓度的T0901317处理CaOV3细胞24小时可显著抑制细胞增殖，明显提高caspase活性并增加凋亡细胞数量[5]。
在体内，连续7周以50mg/kg/day剂量的口服给药T0901317可减轻小鼠主动脉缩窄后的心脏肥大并改善血流动力学功能[6]。对雄性db/db小鼠以50mg/kg/day剂量的腹腔注射T0901317，持续12天，会导致高甘油三酯血症并加重肝脏甘油三酯蓄积[7]。通过胃管灌胃给予11周龄APP23小鼠50mg/kg/day剂量的T0901317连续6天，可显著增加ABCA1表达并降低可溶性淀粉样前体蛋白(APP)水平[8]。