Glycogen Phosphorylase Inhibitor
(Synonyms: GPI) 目录号 : GC43777
An inhibitor of glycogen phosphorylase
Cas No.:648926-15-2
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');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Glycogen phosphorylase in the liver, muscle, and brain initiate glycogenolysis by releasing glucose-1-phosphate from glycogen. Glycogen phosphorylase inhibitor is a cell-permeable acyl urea first identified as an inhibitor of human liver glycogen phosphorylase (IC50 = 53 nM). It blocks glucagon-induced hepatic glycogenolysis in vivo. Glycogen phosphorylase inhibitor has been used to study glycogen utilization in human liver HepG2 cells, retinal explants, and human T lymphocyte Kit 225 cells.
| Cas No. | 648926-15-2 | SDF | |
| 别名 | GPI | ||
| Canonical SMILES | FC1=C(F)C=C(C(NC(NC2=C(OC)C=CC(NC(NC)=O)=C2)=O)=O)C(Cl)=C1 | ||
| 分子式 | C17H15ClF2N4O4 | 分子量 | 412.8 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 5 mg/ml | 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 | 2.4225 mL | 12.1124 mL | 24.2248 mL |
| 5 mM | 0.4845 mL | 2.4225 mL | 4.845 mL |
| 10 mM | 0.2422 mL | 1.2112 mL | 2.4225 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。
Computation as a tool for Glycogen Phosphorylase Inhibitor design
Mini Rev Med Chem 2010 Oct;10(12):1156-74.PMID:20716053DOI:10.2174/1389557511009011156.
Glycogen phosphorylase is an important therapeutic target for the potential treatment of type 2 diabetes. The importance of computation in the search for potent, selective and drug-like glycogen phosphorylase inhibitors which may eventually lead to antihyperglycemic drugs is now firmly established. Acting solo or more effectively in combination with experiment in a multidisciplinary approach to structure based drug design, current day modeling methods are an effective means of reducing the time and money spent on costly experimental procedures. Glycogen phosphorylase is an allosteric protein with five different ligand binding sites, hence offering multiple opportunities for modulation of enzyme activity. However, the binding sites have their own individual characteristics, so that different modeling approaches may be more effective for each. This review is focused on advances in the modelling and design of new inhibitors of the enzyme aimed towards providing the reader with some useful hints towards more successful computer-aided inhibitor (drug) design targeting glycogen phosphorylase.
Advances in Glycogen Phosphorylase Inhibitor design
Curr Opin Investig Drugs 2008 Apr;9(4):379-95.PMID:18393105doi
The regulation of glycogen metabolism is a major therapeutic strategy for blood glucose control in type 2 diabetes. Because glycogen phosphorylase catalyzes the first step in the phosphorolysis of glycogen, it has become a potential key target for controlling hyperglycemia in this disease. This review focuses on advances in new, mostly synthetic, molecules that inhibit glycogen phosphorylase, and describes progress in our understanding of the mechanism of action of these inhibitors gained through X-ray crystallographic studies.
Glycogen Phosphorylase Inhibitor, 2,3-bis[(2E)-3-(4-hydroxyphenyl)prop-2-enamido] butanedioic acid (BF142), improves baseline insulin secretion of MIN6 insulinoma cells
PLoS One 2020 Sep 22;15(9):e0236081.PMID:32960890DOI:10.1371/journal.pone.0236081.
Type 2 diabetes mellitus (T2DM), one of the most common metabolic diseases, is characterized by insulin resistance and inadequate insulin secretion of β cells. Glycogen phosphorylase (GP) is the key enzyme in glycogen breakdown, and contributes to hepatic glucose production during fasting or during insulin resistance. Pharmacological GP inhibitors are potential glucose lowering agents, which may be used in T2DM therapy. A natural product isolated from the cultured broth of the fungal strain No. 138354, called 2,3-bis(4-hydroxycinnamoyloxy)glutaric acid (FR258900), was discovered a decade ago. In vivo studies showed that FR258900 significantly reduced blood glucose levels in diabetic mice. We previously showed that GP inhibitors can potently enhance the function of β cells. The purpose of this study was to assess whether an analogue of FR258900 can influence β cell function. BF142 (Meso-Dimethyl 2,3-bis[(E)-3-(4-acetoxyphenyl)prop-2-enamido]butanedioate) treatment activated the glucose-stimulated insulin secretion pathway, as indicated by enhanced glycolysis, increased mitochondrial oxidation, significantly increased ATP production, and elevated calcium influx in MIN6 cells. Furthermore, BF142 induced mTORC1-specific phosphorylation of S6K, increased levels of PDX1 and insulin protein, and increased insulin secretion. Our data suggest that BF142 can influence β cell function and can support the insulin producing ability of β cells.
[Glycogen Phosphorylase Inhibitor ameliorates pentylenetetrazole-induced acute seizure, neuroinflammation and memory impairment in rats]
Zhongguo Ying Yong Sheng Li Xue Za Zhi 2022 Sep;38(5):406-411.PMID:37088742DOI:10.12047/j.cjap.6283.2022.076.
Objective: In the present study, we determined whether the glycogen phosphorylase(GP)inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) ameliorates pentylenetetrazole (PTZ)-induced acute seizure, neuroinflammation and memory impairment in rats. Methods: In experiment 1, rats were randomly divided into the Vehicle (n=5) and PTZ (n=5) groups, and received intraperitoneal injection of saline or PTZ (70 mg/kg), respectively. Hippocampal tissues were collected 30 min after drug injection. Western blot was used to examine the levels of GP expression. Colorimetric assay was used to determine the levels of lactate. In experiment 2, rats were randomly divided into the Vehicle+Vehicle (n=18), DAB+Vehicle (n=18), Vehicle+PTZ (n=19) and DAB+PTZ (n=18) groups. Rats received intracerebroventricular injection of PBS or DAB (50 μg/2 μl) 15 min before receiving intraperitoneal injection of saline or PTZ (70 mg/kg). Behavioural assays and the Racine scale were used to evaluate seizure severity. Western blot was used to examine the levels of targeted protein of hippocampal tissues. Novel object recognition test was used to assess memory performance. Results: ① Compared with the Vehicle group, the levels of GP and lactate in the hippocampal tissues of the PTZ group were increased significantly (both P＜0.01). ② Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of myoclonic body jerk latency, forelimb clonus latency and tonic-clonic seizure latency were increased significantly (all P＜0.01), while the duration of seizure and seizure scores were decreased significantly (both P＜0.01). ③ Compared with the Vehicle+Vehicle group, in the Vehicle +PTZ group, the levels of IL-1β, IL-6, TNF-α, IBA-1 and GFAP in the hippocampal tissues were increased significantly (all P＜0.01), and the discrimination index in the novel object recognition test was decreased significantly (P＜0.01). Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of IL-1β, TNF-α, IBA-1 and GFAP in the hippocampal tissues were decreased significantly (all, P＜0.01), while the discrimination index in the novel object recognition test was increased significantly (P＜0.01). Conclusion: DAB ameliorates PTZ-induced seizure, neuroinflammation and memory impairment in rats, suggesting that DAB may serve as a novel agent for potential clinical treatment of epilepsy.
Effects of Intracerebroventricular Glycogen Phosphorylase Inhibitor CP-316,819 Infusion on Hypothalamic Glycogen Content and Metabolic Neuron AMPK Activity and Neurotransmitter Expression in Male Rat
J Mol Neurosci 2020 May;70(5):647-658.PMID:31925707DOI:10.1007/s12031-019-01471-0.
Brain glycogen is a vital energy source during metabolic imbalance. Metabolic sensory neurons in the ventromedial hypothalamic nucleus (VMN) shape glucose counter-regulation. Insulin-induced hypoglycemic (IIH) male rats were infused icv with the glycogen breakdown inhibitor CP-316,819 (CP) to investigate whether glycogen-derived fuel controls basal and/or hypoglycemic patterns of VMN gluco-regulatory neuron energy stability and transmitter signaling. CP caused dose-dependent amplification of basal VMN glycogen content and either mobilization (low dose) or augmentation (high dose) of this depot during IIH. Drug treatment also prevented hypoglycemic diminution of tissue glucose in multiple structures. Low CP dose caused IIH-reversible augmentation of AMPK activity and glutamate decarboxylase (GAD) protein levels in laser-microdissected VMN GABA neurons, while the higher dose abolished hypoglycemic adjustments in these profiles. VMN steroidogenic factor-1 (SF-1) neurons exhibited suppressed (low CP dose) or unchanged (high CP dose) basal SF-1 expression and AMPK refractoriness of hypoglycemia at each dose. CP caused dose-proportionate augmentation of neuronal nitric oxide synthase protein and enhancement (low dose) or diminution (high dose) of this profile during IIH; AMPK activity in these cells was decreased in high dose-pretreated IIH rats. CP exerted dose-dependent effects on basal and hypoglycemic patterns of glucagon, but not corticosterone secretion. Results verify that VMN GABA, SF-1, and nitrergic neurons are metabolic sensory in function and infer that these populations may screen unique aspects of neurometabolic instability. Correlation of VMN glycogen augmentation with attenuated hypoglycemic VMN gluco-regulatory neuron AMPK activity implies that expansion of this fuel reservoir preserves cellular energy stability during this metabolic threat.