AMG-3969
目录号 : GC19029
AMG-3969 是一种有效的葡萄糖激酶-葡萄糖激酶调节蛋白相互作用 (GK-GKRP) 破坏剂，IC50 为 4 nM。
Cas No.:1361224-53-4
Sample solution is provided at 25 µL, 10mM.
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AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.
AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 uM and IC50 of 4 nM[1], [2]. It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes)[3].
AMG-3969 has good in vivo pharmacokinetic (PK) properties in rats (75%) and significantly lowers blood glucose levels in a dose-dependent manner db/db mice[1]. AMG-3969 (100 mg/kg) demonstrates significant reductions in blood glucose with robust efficacy (56% reduction) observed at the 8 h time point[2]. AMG-3969 demonstrates dose-dependent efficacy in three models of diabetes: diet induced obese (DIO), ob/ob and db/db mice; however,AMG-3969 is ineffective in lowering blood glucose in normoglycaemic C57BL/6 (B6) mice. AMG-3969 is highly effective in promoting carbohydrate substrate. AMG-3969 exhibits extended changes to carbohydrate oxidation as observed by increased respiratory exchange ratio into the next night and day after a single dose[3].
References:
[1]. Lloyd DJ, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40.
[2]. Nishimura N, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series. J Med Chem. 2014 Apr 10;57(7):3094-116.
[3]. St Jean DJ Jr, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles. J Med Chem. 2014 Jan 23;57(2):325-38.
Animal experiment: | Mice: Diabetic db/db mice are used in the study. At 8:00 AM, mice are bled via retro-orbital sinus puncture and blood glucose values are determined and used to randomize the animals in which their averages are similar, and only mice with blood glucose ranges between 300 and 500 mg/dL are included. Vehicle (2% hydroxypropyl methycellulose, 1% Tween 80, pH 2.2 adjusted with MSA) or AMG-3969 (10, 30, 100 mg/kg) are gavaged at 9:00 AM. Blood glucose is measured at 4, 6, or 8 h posttreatment. At each time point, a 15 μL sample of whole blood is analyzed for drug exposure[2]. |
References: [1]. Lloyd DJ, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40. | |
| Cas No. | 1361224-53-4 | SDF | |
| Canonical SMILES | CC#C[C@@H]1N(C2=CC=C(C(C(F)(F)F)(O)C(F)(F)F)C=C2)CCN(S(=O)(C3=CN=C(N)C=C3)=O)C1 | ||
| 分子式 | C21H20F6N4O3S | 分子量 | 522.46 |
| 溶解度 | DMSO : ≥ 100 mg/mL (191.40 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 | 1.914 mL | 9.5701 mL | 19.1402 mL |
| 5 mM | 0.3828 mL | 1.914 mL | 3.828 mL |
| 10 mM | 0.1914 mL | 0.957 mL | 1.914 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