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.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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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]. |
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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. |
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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. |
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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.
| 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。 |
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| 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 | |||
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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。
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.PMID:27508871DOI:10.1016/j.cmet.2016.07.016
The development of LXR agonists for the treatment of coronary artery disease has been challenged by undesirable properties in animal models. Here we show the effects of an LXR agonist on lipid and lipoprotein metabolism and neutrophils in human subjects. BMS-852927, a novel LXR尾-selective compound, had favorable profiles in animal models with a wide therapeutic index in cynomolgus monkeys and mice. In healthy subjects and hypercholesterolemic patients, reverse cholesterol transport pathways were induced similarly to that in animal models. However, increased plasma and hepatic TG, plasma LDL-C, apoB, apoE, and CETP and decreased circulating neutrophils were also evident. Furthermore, similar increases in LDL-C were observed in normocholesterolemic subjects and statin-treated patients. The primate model markedly underestimated human lipogenic responses and did not predict human neutrophil effects. These studies demonstrate both beneficial and adverse LXR agonist clinical responses and emphasize the importance of further translational research in this area.