| Identification | Back Directory | [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 | [CAS]
1469284-79-4 | [Synonyms]
PF-06424439
PF-06424439 >=98% (HPLC)
PF-06424439 methanesulfonate
[(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 | [Molecular Formula]
C23H30ClN7O4S | [MDL Number]
MFCD28137684 | [MOL File]
1469284-79-4.mol | [Molecular Weight]
536.047 |
| Chemical Properties | Back Directory | [storage temp. ]
room temp | [solubility ]
H2O: soluble10mg/mL, clear | [form ]
powder | [color ]
white to light brown | [Optical Rotation]
[α]/D +7 to +11°, c =1.0 in methanol | [Water Solubility ]
H2O: 10mg/mL, clear | [InChIKey]
ZSTFDNQQOJUJFL-XFULWGLBSA-N | [SMILES]
O=C([C@@H]1CCCN(C2=NC(NC(C3(CC3)N4N=CC(Cl)=C4)=N5)=C5C=C2)C1)N6CCCC6.CS(=O)(O)=O |
| Hazard Information | Back Directory | [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.
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| [storage]
Store at -20°C | [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 |
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