T0901317
(Synonyms: N-(2,2,2-三氟乙基)-N-[4-[2,2,2-三氟-1-羟基-1-(三氟甲基)乙基]苯基]苯磺酰胺) 目录号 : GC10596
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。
Cas No.:293754-55-9
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | A549 cell |
Preparation Method | A549 cells were maintained in RPMI-1640 medium supplemented with 10% FBS, 100U/ml penicillin, and 100U/ml streptomycin at 37°C with 5% CO2. Cell migration was assessed by using a scratch assay. Cells were treated with gefitinib (5μM) and T0901317 (5μM) alone or in combination. 24h later, aliquots of the cells were seeded in 6-well plates and covered with the media. The rest of the cells were resuspended (2×105 cells/well) in 200μl of serum-free media, and then added to the upper compartment of transwell chambers. Next, a 200-μl pipette tip was used to scratch the surface of the plates. Cell migration was detected at 0 and 24h by an optical microscope (magnification, ×100). All experiments were performed in triplicate. The invasion ability of A549 cells was detected using transwell migration chambers. The remaining cells were resuspended (2×105 cells/well) in 200μl of serum-free media, and then added to the upper compartment of transwell chambers. The lower chambers were added with 500μl RPMI-1640 and 20% FBS. The cells in the upper chambers were wiped away using cotton wool after 48h, and the migrated cells in the lower chamber were fixed with 4% paraformaldehyde and then stained with a crystal violet solution. Then, the fixed cells were counted using a light microscope at a magnification of ×100. All experiments were repeated 3 times. |
Reaction Conditions | 5μM; 24h |
Applications | T0901317 treatment significantly inhibited the migration and invasion of A549 cells. |
| Animal experiment [2]: | |
Animal models | APP23 mice |
Preparation Method | For pharmacological studies, eleven-week-old APP23 mice were administered by gastric gavage with 50mg/kg/day of T0901317 in propylene glycol/Tween 80 (4/1) for 6 days or vehicle only. At the end of the treatment period, mice were perfused with 100ml of phosphate-buffered saline, pH 7.4, and the brains were removed and immediately placed on dry ice. Brains (150mg/ml of buffer) were homogenized in Tris/sucrose buffer (250mM sucrose, 20mM Tris base, 1mM EDTA, 1mM EGTA, pH 7.4). Protein extracts were prepared by diluting the initial homogenate 1: 1 in RIPA buffer (10mM Tris/HCl, pH 7.3, 1mM MgCl2, 0.25% SDS, and 1% Triton X-100) in the presence of protease inhibitors (10μg/ml leupeptin, 10μg/ml aprotinin, and 10μg/ml AEBSF) and Western blots were performed for ABCA1 and full-length amyloid precursor protein (APP). |
Dosage form | 50mg/kg/day for 6 days; p.o. |
Applications | Treatment with T0901317 significantly increased the expression of ABCA1 and decreased the ratio of soluble APP (sAPP)β to sAPPα cleavage products. |
References: | |
| Cas No. | 293754-55-9 | SDF | |
| 别名 | N-(2,2,2-三氟乙基)-N-[4-[2,2,2-三氟-1-羟基-1-(三氟甲基)乙基]苯基]苯磺酰胺 | ||
| 化学名 | N-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyl]-N-(2,2,2-trifluoroethyl)benzenesulfonamide | ||
| Canonical SMILES | C1=CC=C(C=C1)S(=O)(=O)N(CC(F)(F)F)C2=CC=C(C=C2)C(C(F)(F)F)(C(F)(F)F)O | ||
| 分子式 | C17H12F9NO3S | 分子量 | 481.33 |
| 溶解度 | ≥ 24.05mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0776 mL | 10.3879 mL | 20.7758 mL |
| 5 mM | 415.5 μL | 2.0776 mL | 4.1552 mL |
| 10 mM | 207.8 μL | 1.0388 mL | 2.0776 mL |
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动物数量 | 只 |
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2.
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- Purity: >99.50%
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