PF-04991532
目录号 : GC31514
PF-04991532是一种有效的肝选择性葡萄糖激酶激活剂，在人类和大鼠中的EC50值分别为80和100nM。
Cas No.:1215197-37-7
Sample solution is provided at 25 µL, 10mM.
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PF-04991532 is a potent, hepatoselective glucokinase activator with EC50s of 80 and 100 nM in human and rat, respectively.
PF-04991532 is a potent, hepatoselective glucokinase activator with EC50s of 80 nM in human and 100 nM in rat and also a Phase 2 clinical candidate. Mechanistic experiments conducted in freshly isolated primary rat hepatocytes treated for 1 hour with PF-04991532 show increased 2-[14C]-deoxyglucose uptake (EC50 =1.261 µM) and increased glucose oxidation (EC50=5.769 µM). Additionally, PF-04991532 decreases the production of glucose from 1-[14C]-lactate in a dose dependent manner (EC50 =0.626 µM). In isolated rat hepatocytes, PF-04991532 increases the expression of G6Pase compare to cells treated only with 100 nM glucagon, and the greatest increase in G6Pase mRNA expression is in the presence of 25 mM glucose, 100 nM glucagon and PF-04991532[1].
A single dose of PF-04991532 increases the glucose infusion rate in order to maintain hyperglycemia. Despite the elevations in plasma triglycerides, surprisingly, hepatic triglycerides in rats dosed with 19 days of PF-04991532 are identical to vehicle treated GK rats. In an additional cohort treated for 28 days, identical hepatic lipid concentrations are observed between vehicle and rats dosed with PF-04991532 (Vehicle: 9.89±0.31; PF-04991532 100 mg/kg: 9.91±0.31). In rats treated with PF-04991532, there is increased expression of lipogenic gene expression such as acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY), and fatty acid synthase (FAS)[1].
[1]. Erion DM, et al. The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. PLoS One. 2014 May 23;9(5):e97139.
Cell experiment: | Primary rat hepatocytes are used to determine the expression of G6Pase. 50,000 freshly isolated rat hepatocytes are incubated in Williams E media overnight supplemented with 100 nM dexamethasone, 1×ITS, and 1×PenStrep. The following morning the media is aspirated, and changed to DMEM no glucose media supplemented with either 5 mM glucose, 25 mM glucose, 1 µM insulin, 100 nM glucagon, or 10 µM PF-04991532. Following 2 hours the media is aspirated, washed twice, and 100 µL of RLT is added to the cells. RNA is extracted with a RNeasy kit[1]. |
Animal experiment: | 13 week old male Goto Kakizaki rats with in-dwelling carotid artery and jugular vein catheters are used in this study. Surgeries are performed one day before shipping. Upon arrival, animals are individually housed, allowed ad libitum chow, and acclimated to their new environment for 6 to 7 days. Animals are randomly assigned either a 100 mg/kg PF-04991532 treatment or vehicle control treatment and orally gavaged at 5 mL/kg. On the day of the experiment, 0.5% Methyl cellulose vehicle is used in vehicle-treated rats. Studies are performed in unstressed, awake, chronically catheterized rats using the insulin clamp technique, in combination with [3-3H] glucose. At the end of the in vivo studies, rats are euthanized[1]. |
References: [1]. Erion DM, et al. The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. PLoS One. 2014 May 23;9(5):e97139. | |
| Cas No. | 1215197-37-7 | SDF | |
| Canonical SMILES | O=C(C1=CC=C(NC([C@@H](N2C=C(C(F)(F)F)N=C2)CC3CCCC3)=O)N=C1)O | ||
| 分子式 | C18H19F3N4O3 | 分子量 | 396.36 |
| 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 | 2.523 mL | 12.6148 mL | 25.2296 mL |
| 5 mM | 0.5046 mL | 2.523 mL | 5.0459 mL |
| 10 mM | 0.2523 mL | 1.2615 mL | 2.523 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
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet