Powder: -20°C for 3 years | In solvent: -80°C for 1 year
SR3335 (ML 176) 是特异性RORα反向激动剂,能够与 RORα直接结合,其Ki=220 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 296 | 现货 | ||
5 mg | ¥ 690 | 现货 | ||
10 mg | ¥ 1,260 | 现货 | ||
25 mg | ¥ 2,150 | 现货 | ||
50 mg | ¥ 3,190 | 现货 | ||
100 mg | ¥ 4,680 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 697 | 现货 |
产品描述 | SR3335 (ML 176) is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM). |
靶点活性 | RORα:220 nM(ki) |
体外活性 | KHS101 increased neuronal differentiation of adherently cultured rat NPCs in a dose-dependent fashion (EC50 ~ 1 μM). KHS101-induced neuron formation (40–60% TuJ1+ cells at 1.5–5 μM KHS101) was also observed under neurosphere-forming conditions in secondary neurospheres derived from both the hippocampus and the subventricular zone (SVZ) of adult rats [1]. In HCC cell lines, KHS101 suppressed cell growth and sphere formation as well as the expression of stem cell transcription factors, including Bmi1, c-Myc, and Nanog. Silencing TACC3 may suppress the Wnt/β-catenin and PI3K/AKT signaling pathways, which regulate cancer stem cell-like characteristics [2]. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101 promoted aggregation of proteins regulating mitochondrial integrity and energy metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were selectively impaired in KHS101-treated GBM cells [3]. |
体内活性 | In two intracranial patient-derived xenograft tumor models in mice, systemic administration of KHS101 reduced tumor growth and increased survival without discernible side effects. The doses of 6 mg/kg KHS101 (i.v. and s.c.) resulted in reasonable plasma concentrations (>1.5 μM) with a plasma half-life of 1.1–1.4 h, and relative bioavailability of 69% following s.c. dosing. Most importantly, the distribution of KHS101 to the brain was extensive as demonstrated by a brain-to-plasma AUC(0–3h) ratio of ~8 (dosing: 3 mg/kg KHS101, i.v.) [3]. |
细胞实验 | Rat NPCs were derived and cultured as described previously by others. After hippocampal cell isolation, the number of dissociated cells was determined and ~5 × 10^5 cells were plated in 60-mm uncoated plates. After overnight incubation (37 °C, 5% CO2, and 95% humidity), the medium was changed and the cells were expanded and maintained in an undifferentiated state on polyornithine- (10 μg/mL in water) and laminin-coated (5 μg/mL in PBS;) dishes in DMEM/F12 supplemented with N2 and basic fibroblast growth factor (bFGF, 20 ng/mL;). For KHS101 and shRNA-induction experiments, early passage cells (passaged no more than six times after hippocampal isolation) were trypsinized and plated at a density of ~1,000 cells/cm2 into N2 medium (DMEM/F12 supplemented with N2) containing KHS analogs (e.g., KHS101, KHS92, and NP; SI Text) at different concentrations (0.5–5 μM) or DMSO (0.1%), RA (1–2 μM), BDNF (100 ng/mL), and/or BMP4 (50–100 ng/mL) for 4 d [1]. |
动物实验 | To investigate the pharmacokinetic properties of KHS101, male Sprague–Dawley rats were administered 3 mg/kg KHS101 i.v. or s.c. One rat was killed per time point at 5 min, 40 min, 1 h, and 3 h after dosing, and samples of blood (100 μL) and whole brains were collected. In a separate study, rats were administered 6 mg/kg KHS101 i.v. or s.c. Five blood samples of 100 μL each were collected serially via a jugular vein catheter at 2 min (i.v. only), 0.5 h (s.c. only), and 1, 3, 7 and 24 h after dosing. Plasma and homogenized whole brain samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). To study neuronal differentiation upon KHS101 administration in vivo, adult Fisher 344 rats (~10 wk old) received s.c. injections of 6 mg/kg KHS101 or vehicle control (5% ethanol in 15% Captisol). All rats received one daily i.p. injection of 200 mg/kg BrdU for 6 consecutive days after the first day. After 14 d, the animals were killed and perfusion fixed, and the brains were removed and subjected to immunohistochemical analysis [1]. |
别名 | ML 176 |
分子量 | 405.34 |
分子式 | C13H9F6NO3S2 |
CAS No. | 293753-05-6 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 30 mg/mL
DMSO: 50 mg/mL (123.35 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.4671 mL | 12.3353 mL | 24.6706 mL | 61.6766 mL |
5 mM | 0.4934 mL | 2.4671 mL | 4.9341 mL | 12.3353 mL | |
10 mM | 0.2467 mL | 1.2335 mL | 2.4671 mL | 6.1677 mL | |
20 mM | 0.1234 mL | 0.6168 mL | 1.2335 mL | 3.0838 mL | |
50 mM | 0.0493 mL | 0.2467 mL | 0.4934 mL | 1.2335 mL | |
100 mM | 0.0247 mL | 0.1234 mL | 0.2467 mL | 0.6168 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
SR3335 293753-05-6 Metabolism ROR RAR-related orphan receptor ML 176 inhibit Inhibitor SR-3335 ML-176 SR 3335 ML176 inhibitor