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PF-04620110
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
PF-04620110图片
CAS NO:1109276-89-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
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500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)396.44
FormulaC21H24N4O4
CAS No.1109276-89-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 49 mg/mL (123.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Other InfoChemical Name: trans-4-[4-(4-Amino-7,8-dihydro-5-oxopyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]-cyclohexaneacetic acid
InChi Key: GEVVQZHMFVFGLN-HDJSIYSDSA-N
InChi Code: InChI=1S/C21H24N4O4/c22-19-18-20(24-12-23-19)29-10-9-25(21(18)28)16-7-5-15(6-8-16)14-3-1-13(2-4-14)11-17(26)27/h5-8,12-14H,1-4,9-11H2,(H,26,27)(H2,22,23,24)/t13-,14-
SMILES Code: O=C(O)C[C@H]1CC[C@H](C2=CC=C(N3CCOC4=NC=NC(N)=C4C3=O)C=C2)CC1
SynonymsPF04620110. PF-4620110; PF-04620110; PF 04620110; PF 4620110; PF4620110.
实验参考方法
In Vitro

In vitro activity: PF-04620110 is an orally active, selective and potent diglyceride acyltransferase-1 (DGAT1) inhibitor with IC50 of 19 NM.


Kinase Assay: 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 Assay: PF-04620110 (IC50 39 nM) inhibits the incorporation of 3H-glycerol into TG.

In VivoIn Rats, PF-04620110 reduces plasma triglyceride levels t doses of ≥0.1 mg/kg following a lipid challenge. DGAT1 inhibition by PF-04620110 causes an enrichment of polyunsaturated fatty acids within the TG class of lipids in rodents.
Animal modelMale Sprague Dawley rats
Formulation & DosageDissolved in water; 10 mg/kg; p.o.
References

ACS Med Chem Lett. 2011 Mar 18;2(5):407-12; Am J Physiol Gastrointest Liver Physiol. 2013 Jun 1;304(11):G958-69.