Nemiralisib
(Synonyms: GSK2269557 (free base)) 目录号 : GC36714
Nemiralisib, also known as GSK-2269557, is a potent and selective PI3Kδ inhibitor(pKi = 9.9).
Cas No.:1254036-71-9
Sample solution is provided at 25 µL, 10mM.
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Nemiralisib, also known as GSK-2269557, is a potent and selective PI3Kδ inhibitor(pKi = 9.9).
GSK-2269557 has low oral bioavailability (F=2%) and in vivo clearance of 28 mL/min/kg but has a high volume of distribution of 6.3 L/kg. GSK-2269557 induces concentration-dependent increases in QT interval and Tp-e at 0.3 and 1 μM (1 and 0.5 Hz) and an increase in QRS at 1 μM (2 Hz), however, no treatment-related torsades de pointes (TdP) arrhythmias are observed. In a disease relevant brown Norway rat acute OVA model of Th2 driven lung inflammation, GSK-2269557 is shown to protect against eosinophil recruitment with an ED50 of 67 μg/kg and dose-dependently reduces recruitment of all leukocyte subpopulations and IL-13 in the lungs[1].
[1] Down K, et al. J Med Chem. 2015, 58(18):7381-99.
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Animal experiment: |
Rats[1]In vivo pharmacokinetics is tested in Sprague Dawley male rats. Compounds (e.g., Nemiralisib) are administered discretely by the oral or intravenous routes, at a dose level of 3 and 1 mg/kg respectively (n=2 rats/route). Compounds (e.g., Nemiralisib) are formulated as a solution in DMSO:PEG200:water (5:45:50 v/v/v) at a dose volume of 6 (oral) and 2 (intravenous) mL/kg. All animals are serially bled from the tail vein and blood samples collected over a time-course of 0-7 h are submitted to LC-MS/MS analysis for the quantification of the parent compound. The main pharmacokinetic parameters are estimated by non-compartmental analysis. |
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References: [1]. Down K et al. Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease.J Med Chem. 2015 Sep 24;58(18):7381-99. |
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| Cas No. | 1254036-71-9 | SDF | |
| 别名 | GSK2269557 (free base) | ||
| Canonical SMILES | CC(N1CCN(CC2=CN=C(C3=CC(C4=CC=CC5=C4C=CN5)=CC6=C3C=NN6)O2)CC1)C | ||
| 分子式 | C26H28N6O | 分子量 | 440.54 |
| 溶解度 | DMSO: 33.33 mg/mL (75.66 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 | 2.2699 mL | 11.3497 mL | 22.6994 mL |
| 5 mM | 0.454 mL | 2.2699 mL | 4.5399 mL |
| 10 mM | 0.227 mL | 1.135 mL | 2.2699 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet