XL041 (BMS-852927)
(Synonyms: BMS-852927) 目录号 : GC32459
XL041 (BMS-852927) (BMS-852927) 是一种 LXRβ-选择性激动剂。
Cas No.:1256918-39-4
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
BMS-852927 is an LXRβ-selective agonist.
BMS-852927 is an LXRβ-selective agonist with 20% LXRα and 88% LXRβ activity compared to a full pan agonist in transactivation assays. BMS-852927 is potent, with an EC50=9 nM and 26% activity in an in vitro human whole-blood endogenous target gene activation assay (WBA). BMS-852927 has similar binding affinity to LXRα and LXRβ (19 and 12 nM, respectively)[1].
BMS-852927, has a very favorable profile at efficacious doses in cynomolgus monkeys and mice. BMS-852927 pre-treatment of C57BL/6J mice for 7 days results in potent, dose-dependent stimulation of cholesterol efflux in this system, reaching a maximum in the 3 mg/kg/day dose group of 70% above vehicle in the initial efflux rate. Similar results are obtained in LDLR knockout (KO) mice. In a separate study, BMS-852927 inhibits the progression of atherosclerosis in a 12 week study in LDLR KO mice. Importantly, the dose response for inhibition of atherosclerosis (0.1-3 mg/kg/day) is similar to the dose response for macrophage reverse cholesterol transport (RCT) stimulation (0.03-3 mg/kg/day), a major underlying mechanism through which LXR agonists affect the disease[1].
[1]. Kirchgessner TG, et al. Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils. Cell Metab. 2016 Aug 9;24(2):223-33.
|
Kinase experiment: |
Peritoneal macrophages are prepared from male C57BL/6 mice that are stimulated with 4% thioglycolate for 4 days. Macrophages are cultured in DMEM supplemented with 20% FBS and 100 U/mL antibiotic-antimycotic. Macrophages are incubated with LXR agonists (eg, XL041) in serum-free DMEM for 20hrs, followed by 5hr treatment of LPS (20 ng/mL). The effect of agonists on IL-23α and Mertk mRNAs is determined[1]. |
|
Animal experiment: |
Mice[1] To study effects of LXR agonists on neutrophils, C57BL/6 mice pre-acclimated to oral dosing (n=8/group) are randomly assigned to vehicle; 0.03, 0.1, 1, or 3 mg/kg/day XL041; and 0.3 or 3 mg/kg/day GW3965 and dosed orally for 3 days. Following anesthesia with isoflurane, blood is collected by retro-orbital bleeding and analyzed for neutrophil levels using an Advia hematology instrument employing peroxidase staining. Monkeys[1] All studies are performed in male animals. In a PD study, animals are randomized into six treatment groups (n=3/group) and dosed once daily with vehicle, 10 mg/kg/day T0901317, and 0.1, 0.3, 1, or 3 mg/kg/day XL041 for 14 days. Blood RNA and plasma lipids are determined at baseline and days 1, 4, 7, and 14 of dosing for the pharmacodynamic (PD)study, and on days 1 and 7 for the liver triglyceride (TG) magnetic resonance spectroscopy (MRS) study. |
|
References: [1]. Kirchgessner TG, et al. Beneficial and Adverse Effects of an LXR Agonist on Human Lipid and Lipoprotein Metabolism and Circulating Neutrophils. Cell Metab. 2016 Aug 9;24(2):223-33. |
|
| Cas No. | 1256918-39-4 | SDF | |
| 别名 | BMS-852927 | ||
| Canonical SMILES | OC(C)(C)C1=CN(C2=CC=C(C3=CC(S(=O)(C)=O)=C(CO)C(F)=C3)C=C2F)C(C(C)(C4=C(Cl)C=CC=C4Cl)C)=N1 | ||
| 分子式 | C29H28Cl2F2N2O4S | 分子量 | 609.51 |
| 溶解度 | DMSO : ≥ 150 mg/mL (246.10 mM) | 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。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6407 mL | 8.2033 mL | 16.4066 mL |
| 5 mM | 0.3281 mL | 1.6407 mL | 3.2813 mL |
| 10 mM | 0.1641 mL | 0.8203 mL | 1.6407 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet