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[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate

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[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate Basic information

Product Name:
[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate
Synonyms:
  • PF-06424439
  • [(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate
  • PF-06424439 methanesulfonate
  • PF-06424439 >=98% (HPLC)
  • acyl-CoA:cholesterol acyltransferase,Inhibitor,Acyltransferase,mono- acylglycerol acyltransferase,PF-06424439,PF 06424439 methanesulfonate,inhibit,Diacylglycerol acyltransferase,PF06424439,Diglyceride acyltransferase,PF06424439 methanesulfonate,PF 06424439
  • (R)-(1-(2-(1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl)-1H-imidazo[4,5-b]pyridin-5-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone methanesulfonate
  • PF-06424439 methanesulfonate, 10 mM in DMSO
  • PF-06424439【PZ0233】
CAS:
1469284-79-4
MF:
C23H30ClN7O4S
MW:
536.0468
Mol File:
1469284-79-4.mol
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[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate Chemical Properties

storage temp. 
room temp
solubility 
H2O: soluble10mg/mL, clear
form 
powder
color 
white to light brown
optical activity
[α]/D +7 to +11°, c =1.0 in methanol
Water Solubility 
H2O: 10mg/mL, clear
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Safety Information

WGK Germany 
3
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[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate Usage And Synthesis

Description

PF-06424439 is an orally bioavailable inhibitor of diacylglycerol acyltransferase 2 (DGAT-2; IC50 = 14 nM). It is selective for DGAT-2 over the related acyltransferases DGAT-1, MGAT-2, and MGAT-3 (IC50s = >50 μM). PF-06424439 (0.1-10 mg/kg) reduces plasma triglyceride levels in sucrose-fed rats in a dose-dependent manner. It also reduces plasma levels of cholesterol and triglycerides as well as hepatic triglycerides in LDL receptor knockout mice fed a high-fat, high-cholesterol diet when administered at a dose of 60 mg/kg per day.

Uses

PF-06424439 has been used as a diacylglycerol acyltransferase 2 (DGAT2)?inhibitor:

  • to study its effects on cell mortality and lipid synthesis in epithelial colon cells and colorectal cancer stem cells
  • to study its effects on HeLa cells
  • to study its inhibitory effects on neutral lipid synthesis in HT-1080 cells

Biochem/physiol Actions

PF-06424439 is a potent and selective inhibitor of diacylglycerol acyltransferase 2 (DGAT2).

in vivo

PF-06424439 methanesulfonate (p.o.; 60 mg/kg/day; for 3 days) reduces plasma TG and cholesterol levels and decreases nonsignificant in circulating lipids in mice (Ldlr-/-)[1].
PF-06424439 methanesulfonate (i.v.; 1 mg/kg) shows moderate clearance in rats following intravenous administration and moderate steady-state volume of distribution (Vdss) results in a short half-life[1].

Animal Model:Male low-density lipoprotein receptor (Ldlr) knockout mice (Ldlr-/-)[1]
Dosage:60 mg/kg
Administration:P.o.; daily; for 3 days
Result:Reduced plasma TG and cholesterol levels and decreased nonsignificant in circulating lipids.
Animal Model:Male Wistar-Han rats[1]
Dosage:1 mg/kg
Administration:I.v.
Result:Showed moderate clearance and a short half-life with t1/2=1.39 h.

storage

Desiccate at RT

References

[1] KENTARO FUTATSUGI*. Discovery and Optimization of Imidazopyridine-Based Inhibitors of Diacylglycerol Acyltransferase 2 (DGAT2)[J]. Journal of Medicinal Chemistry, 2015, 58 18: 7173-7185. DOI: 10.1021/acs.jmedchem.5b01006
[2] A. NIKOLAI VON KRUSENSTIERN. Identification of essential sites of lipid peroxidation in ferroptosis[J]. Nature chemical biology, 2023, 19 6: 719-730. DOI: 10.1038/s41589-022-01249-3

[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonateSupplier

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[(3R)-1-[2-[1-(4-Chloro-1H-pyrazol-1-yl)cyclopropyl]-3H-imidazo[4,5-b]pyridin-5-yl]-3-piperidinyl]-1-pyrrolidinyl-methanone methanesulfonate(1469284-79-4)Related Product Information