PSN-GK1
目录号 : GC31618
PSN-GK1是有效的葡萄糖激酶(glucokinase)活化剂，EC50值为0.13μM。
Cas No.:745051-61-0
Sample solution is provided at 25 µL, 10mM.
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PSN-GK1 is a potent glucokinase activator with an EC50 of 0.13 μM.
PSN-GK1 exhibits an excellent pharmacokinetic profile, with high oral bioavailability, in the rat. PSN-GK1 can markedly reduce blood glucose which accompanied by a trend toward increased pancreatic insulin release. Separately, the antihyperglycemic actions of PSN-GK1 have been shown to be a result of both pancreatic and hepatic effects. In addition, PSN-GK1 engenders potent antihyperglycemic effects in diabetic rodents without causing hypoglycemia[1]. At 5 mM glucose, PSN-GK1 activates glucokinase (4.3-fold, EC50=130 nM), increases MIN6 insulin secretion (26-fold, EC50=267 nM) and 2-DG hepatocytic uptake (3-fold, EC50=1 μM). In C57Bl/6 mice, PSN-GK1 reduces blood glucose at 1 and 10 mg/kg (by mouth), but insulin is increased significantly at only the higher dose. In hyperinsulinaemic 10-mM glucose clamps, PSN-GK1 increases2-DG incorporation into liver glycogen sixfold, directly demonstrating liver effects[2].
[1]. Bertram LS, et al. SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1. J Med Chem. 2008 Jul 24;51(14):4340-5. [2]. Fyfe MC, et al. Glucokinase activator PSN-GK1 displays enhanced antihyperglycaemic and insulinotropic actions. Diabetologia. 2007 Jun;50(6):1277-87.
Kinase experiment: | Glucokinase activity is measured in a coupled reaction with glucose-6-phosphate dehydrogenase (G6PDH) by monitoring NADPH production at A340 in a plate reader after 15 min incubation at 24°C, in a final volume of 100 μL containing 25 mM HEPES pH 7.1, 25 mM KCl, 5 mM glucose, 1 mM ATP, 2 mM MgCl2, 1 mM DL-dithiothreitol, 1 mM NADP, 2.5 U/mL G6PDH, 0.4 μg GST-glucokinase. Ten dilutions of PSN-GK1 from 0.004 to 100 μM are tested, calculating and fitting fold changes in activity vs controls to sigmoidal curves using a four-parameter logistic model[2]. |
Animal experiment: | Mice[2]C57Bl/6J mice Food is withdrawn 5 h before dosing, while water is available throughout. A blood sample is taken from the tail tip under local anaesthetic for glucose and insulin measurement. Thereafter, mice are weighed and dosed orally with PSN-GK1 (1 or 10 mg/kg) or vehicle. Blood samples are taken 15, 30, 60, 120 and 240 min after dosing, samples (20 μL) for glucose being taken into disposable micro-pipettes and added to 480 μL haemolysis reagent[2]. |
References: [1]. Bertram LS, et al. SAR, pharmacokinetics, safety, and efficacy of glucokinase activating 2-(4-sulfonylphenyl)-N-thiazol-2-ylacetamides: discovery of PSN-GK1. J Med Chem. 2008 Jul 24;51(14):4340-5. | |
| Cas No. | 745051-61-0 | SDF | |
| Canonical SMILES | O=C(NC1=NC=C(F)S1)[C@@H](C2=CC=C(S(=O)(C3CC3)=O)C=C2)CC4CCOCC4 | ||
| 分子式 | C20H23FN2O4S2 | 分子量 | 438.54 |
| 溶解度 | Soluble in DMSO | 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 | 2.2803 mL | 11.4015 mL | 22.8029 mL |
| 5 mM | 0.4561 mL | 2.2803 mL | 4.5606 mL |
| 10 mM | 0.228 mL | 1.1401 mL | 2.2803 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet