| CAS |
No.293753-05-6 |
| 英文名称 |
SR3335 |
| 别名 |
ML176;CS-1044;T0507-1786;SR3335; |
| 分子式 |
C13H9F6NO3S2 |
| 分子量 |
405.34 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD02724814 |
| SMILES |
O=S(C1=CC=CS1)(NC2=CC=C(C(C(F)(F)F)(C(F)(F)F)O)C=C2)=O |
| InChIKey |
LZWUNZRMANFRAO-UHFFFAOYSA-N |
| InChI |
InChI=1S/C13H9F6NO3S2/c14-12(15,16)11(21,13(17,18)19)8-3-5-9(6-4-8)20-25(22,23)10-2-1-7-24-10/h1-7,20-21H |
| PubChem CID |
2360837 |
| 靶点 |
RORα |
| 通路 |
Metabolic Enzyme&Protease |
| 背景说明 |
SR3335是选择性的 RORα 反向激动剂。 |
| 生物活性 |
SR3335 (ML 176) is a selective RORα inverse agonist that directly binds to RORα with a Ki of 220 nM.[1-2] |
| IC50 |
Ki: 220 nM (RORα)[1] |
| In Vitro |
SR3335 是一种选择性 RORα 部分反向激动剂。在使用[3H]25-羟基胆固醇作为标记的生化放射性配体结合测定中，很明显未标记的 SR3335 以剂量依赖性方式竞争与 RORα LBD 的结合。使用 Cheng-Prusoff 方程计算 Ki 为 220 nM。在基于细胞的嵌合受体 Gal4 DNA 结合域-NR 配体结合域共转染试验中，SR3335 显著抑制 RORα 的组成型反式激活活性 (IC50=480 nM) (部分反向激动剂活性)，但对LXRα和RORγ的活性没有影响[1]。SR3335 抑制HepG2细胞中参与肝糖异生的内源性RORα靶基因的表达，包括葡萄糖-6-磷酸酶 (G6Pase) 和磷酸烯醇丙酮酸羧激酶 (PEPCK)[2]。SR3335 还可以体外阻断 IL-25 和 IL-33 诱导的 ILC2 增殖和 IL-13 的产生[3]。 |
| In Vivo |
SR3335 在小鼠腹腔注射后表现出合理的暴露。使用饮食诱导的肥胖 (DIO) 小鼠模型评估 SR3335 抑制糖异生的能力，其中小鼠以 15 mg/kg bid、ip 处理 6 天，然后进行丙酮酸耐受性测试。SR3335 处理的小鼠在丙酮酸攻击后显示出较低的血浆葡萄糖水平，这与抑制糖异生作用一致。重要的是，用 SR3335 处理 7 天后，用 SR3335 处理的小鼠体重或食物摄入量没有差异[1]。SR3335 (15 mg/kg/天；ip 7天) 减少未成熟小鼠 (6 日龄 BALB/c 小鼠的 RV 感染) 中鼻病毒 (RV) 诱导的肺 ILC2s[3]。 |
| 细胞实验 |
HEK293 cells are maintained in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 10% fetal bovine serum at 37°C under 5% CO2. HepG2 cells are maintained and routinely propagated in minimum essential medium supplemented with 10% fetal bovine serum at 37°C under 5% CO2. 24 h prior to transfection， cells are plated in 96-well plates at a density of 15×103 cells/well. Transfections are performed using LipofectamineTM 2000. 16 h post-transfection， the cells are treated with vehicle or SR3335. 24 h post-treatment， the luciferase activity is measured using the Dual-GloTM luciferase assay system. The values indicated represent the means±S.E. from four independently transfected wells. The experiments are repeated at least three times[1]. |
| 动物实验 |
Mice[1] 30 week old Diet induced obese (DIO) C57BL/6 male mice are purchased from Jackson Laboratories that are maintained on a 65% Kcal high-fat diet from weaning. DIO mice are treated twice per day (07:00h and 18:00h) with 15 mg/kg SR3335 or vehicle for 6 days i.p. Pyruvate tolerance test is conducted on day 6 of the treatment. Food is removed from mice in the morning after SR3335 injection， fasted for 6 hours and the pyruvate tolerance test is conducted at 13:00h. Time 0 blood glucose is measured taken from the tail nip and the pyruvate challenge is initiated by injection of 2g/kg of pyruvate i.p. followed by measuring blood glucose at 15， 30 and 60 min following the injection. Blood glucose is measured by one touch ultra glucose-meter. |
| 数据来源文献 |
[1]. Kumar N， et al. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist. ACS Chem Biol. 2011 Mar 18;6(3):218-22.
[2]. Rajput C， et al. RORα-dependent type 2 innate lymphoid cells are required and sufficient for mucous metaplasia in immature mice. Am J Physiol Lung Cell Mol Physiol. 2017;312(6):L983-L993. |
| 规格 |
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| 单位 |
瓶 |
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