PF-04620110
(Synonyms: PF 04620110,PF04620110) 目录号 : GC15274A potent, bioavailable inhibitor of DGAT-1
Cas No.:1109276-89-2
Sample solution is provided at 25 µL, 10mM.
PF-04620110 is a potent, selective and orally-bioavailable inhibitor of diacylglycerol acyltransferase 1 (DGAT-1), an enzyme catalyzing the final committed step in the biosynthesis of triglycerides, that inhibits DGAT-1 with values of 50% inhibition concentration IC50 of 19 nM and 8 nM in human and HT-29 cells respectively. PF-04620110 displays a highly selective, more than 100 fold, inhibition against DGAT-1 rather than a range of lipid processing enzymes, including human DGAT-2, human acyl-CoA:cholesterol acyltransferase 1, human acyl-CoA:wax alcohol acyltransferase 1, human acyl-CoA:wax alcohol acyltransferase 2, human acyl-CoA:monacylglycerol acyltransferase 2, human acyl-CoA:monacylglycerol acyltransferase 3 and mouse MGAT 1.
Reference
Lee KR, Choi SH, Song JS, Seo H, Chae YJ, Cho HE, Ahn JH, Ahn SH, Bae MA. Determination of PF-04620110, a novel inhibitor of diacylglycerol acyltransferase-1, in rat plasma using liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic studies. Biomed Chromatogr. 2013; 27(7):846-852.
Robert L. Dow *, Jian-Cheng Li , Michael P. Pence , E. Michael Gibbs , Jennifer L. LaPerle , John Litchfield , David W. Piotrowski , Michael J. Munchhof , Tara B. Manion , William J. Zavadoski , Gregory S. Walker , R. Kirk McPherson , Susan Tapley , Eliot Sugarman , Angel Guzman-Perez , and Paul DaSilva-Jardine Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1. ACS Med. Chem. Lett., 2011, 2 (5), pp 407–412
Kinase experiment [1]: | |
In Vitro Assay for DGAT-1 Enzyme Inhibition: |
Human full-length diacylglycerol:acylCoA acyltransferase 1 (DGAT-1) was expressed in Sf9 insect cells which are then lysed and a crude membrane fraction (105, 000 x g pellet) was prepared. DGAT-1 activity was measured in 384-well format in a total assay volume of 25 μl that contained, Hepes buffer (50 mM, pH7.5), MgCl2 (10 mM), bovine serum albumin (0.6 mg/ml), [14C]decanoylCoA (20 μM, 58 Ci/mol) and membranes (25 μg/ml) into which 1,2 dioleoyl-sn-glycerol (75 μM) in acetone has already been incorporated. Inhibitors in DMSO were pre-incubated with membranes before initiating the DGAT-1 reaction by the addition of decanoylCoA.The reactions were allowed to proceed for 1.5 h at room temperature and then terminated by the addition of 10 μl of HCl (0.5 M). Reaction mixtures were neutralized by the addition of 15 μl of tris(hydroxy-methyl)aminomethane (1M, pH 8.0) and then mixed by trituration with 37.5 μl of Microscint-E . Plates contents were allowed to partition for 15 to 30 min before 14C was measured in a scintillation spectrometer. Percent inhibition of test compounds was computed as 100-(DPM DMSO uninhibited- DPM test compound)/(DPM DMSO uninhibited). |
Cell experiment [1]: | |
Cell lines |
Human intestinal epithelial cells |
Preparation method |
Soluble in DMSO > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions |
5 hours at 37oC |
Applications |
PF-04620110 (IC50 39 nM) inhibits the incorporation of 3H-glycerol into TG. |
Animal experiment [2]: | |
Animal models |
C57BL/6J and B6.129S4-Dgat1tm1Far (DGAT1 knockout mice) male mice (7–12 wk of age) |
Dosage form |
Oral dose of 1, 0.3, 0.1, and 0.01 mg/kg (TG/retinyl palmitate tolerance test) |
Applications |
Administration of a single dose of a DGAT1 inhibitor, PF-04620110, reduces postprandial plasma TG and retinyl palmitate excursions in mice. |
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: 1. Dow RL, Li JC, Pence MP, Gibbs EM, LaPerle JL, Litchfield J, Piotrowski DW, Munchhof MJ, Manion TB, Zavadoski WJ, Walker GS, McPherson RK, Tapley S, Sugarman E, Guzman-Perez A, DaSilva-Jardine P. Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1. ACS Med Chem Lett. 2011 Mar 18;2(5):407-12. 2. Maciejewski BS, LaPerle JL, Chen D, Ghosh A, Zavadoski WJ, McDonald TS, Manion TB, Mather D, Patterson TA, Hanna M, Watkins S, Gibbs EM, Calle RA, Steppan CM. Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans. Am J Physiol Gastrointest Liver Physiol. 2013 Jun 1;304(11):G958-69. |
Cas No. | 1109276-89-2 | SDF | |
别名 | PF 04620110,PF04620110 | ||
化学名 | 2-[4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)phenyl]cyclohexyl]acetic acid | ||
Canonical SMILES | C1CC(CCC1CC(=O)O)C2=CC=C(C=C2)N3CCOC4=NC=NC(=C4C3=O)N | ||
分子式 | C21H24N4O4 | 分子量 | 396.44 |
溶解度 | ≥ 16.9mg/mL 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 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL |
5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL |
10 mM | 0.2522 mL | 1.2612 mL | 2.5224 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: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet