Home>>Signaling Pathways>> Metabolism>> Transferase>>PF-04620110

PF-04620110 (Synonyms: PF 04620110,PF04620110)

Catalog No.GC15274

A potent, bioavailable inhibitor of DGAT-1

Products are for research use only. Not for human use. We do not sell to patients.

PF-04620110 Chemical Structure

Cas No.: 1109276-89-2

Size Price Stock Qty
10mM (in 1mL DMSO)
$59.00
In stock
5mg
$54.00
In stock
10mg
$91.00
In stock
50mg
$364.00
In stock
100mg
$585.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

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.

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

Cas No. 1109276-89-2 SDF
Synonyms PF 04620110,PF04620110
Chemical Name 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
Formula C21H24N4O4 M.Wt 396.44
Solubility ≥ 16.9mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
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
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for PF-04620110

Average Rating: 5 ★★★★★ (Based on Reviews and 30 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for PF-04620110

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.