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SR3335
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SR3335图片
CAS NO:293753-05-6
包装与价格:
包装价格(元)
5 mg电议
10 mg电议
50 mg电议
100 mg电议
1 mL*10 mM(in DMSO)电议

产品名称
ML 176
产品介绍
SR3335 是特异性RORα反向激动剂,能够与 RORα直接结合,其Ki=220 nM。

产品描述

SR 3335 is a selective inverse agonist of RORα, competitively inhibiting the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM).

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].

Cas No.

293753-05-6

分子式

C13H9F6NO3S2

分子量

405.33

别名

ML 176

储存和溶解度

Ethanol:30 mg/mL
DMSO:40 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years