Toggle Nav

PF-04620110

In stock
Catalog No.
A4384
DGAT-1 inhibitor,potent and selective
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$120.00
In stock
5mg
$50.00
In stock
10mg
$96.00
In stock
50mg
$380.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt396.44
Cas No.1109276-89-2
FormulaC21H24N4O4
SynonymsPF 04620110,PF04620110
Solubility≥16.9mg/mL in DMSO, <2.58 mg/mL in EtOH, <2.04 mg/mL in H2O
Chemical Name2-[4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-yl)phenyl]cyclohexyl]acetic acid
SDFDownload SDF
Canonical SMILESC1CC(CCC1CC(=O)O)C2=CC=C(C=C2)N3CCOC4=NC=NC(=C4C3=O)N
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

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.

Biological Activity

Description PF-04620110 is a potent and selective inhibitor of DGAT-1 with IC50 value of 19 nM.
Targets DGAT-1          
IC50 19 nM          

Quality Control

Quality Control & MSDS

View current batch:

Chemical structure

PF-04620110