| Identification | Back Directory | [Name]
Benzenebutanol, β-amino-4-[(3,4-dichlorophenyl)methoxy]-β-methyl-, (βS)- | [CAS]
2748196-63-4 | [Synonyms]
Benzenebutanol, β-amino-4-[(3,4-dichlorophenyl)methoxy]-β-methyl-, (βS)- | [Molecular Formula]
C18H21Cl2NO2 | [MOL File]
2748196-63-4.mol | [Molecular Weight]
354.27 |
| Chemical Properties | Back Directory | [Boiling point ]
516.6±50.0 °C(Predicted) | [density ]
1.258±0.06 g/cm3(Predicted) | [solubility ]
DMF: 30 mg/ml; DMSO: 30 mg/ml; Ethanol: 30 mg/ml | [form ]
A crystalline solid | [pka]
12.84±0.20(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Description]
P053 is an inhibitor of ceramide synthase 1 (CerS1; IC50s = 0.54 and 0.46 μM for human and mouse CerS1, respectively).1 It is selective for CerS1 over CerS2, CerS4, CerS5, and CerS6 (IC50s = 28.6, 17.2, 7.2, and 11.4 μM, respectively). P053 decreases the production of C18 ceramide from dihydrosphingosine in cortical neuron cultures in a concentration-dependent manner. It also lowers levels of C18 ceramide, C18 galactosylceramide, and C18:0 and 18:1 sphingomyelin species in HEK293 cells, when used at concentrations ranging from 30 to 300 nM, without inducing cell death. P053 (5 mg/kg) decreases endogenous C18 and C18:2/18:0 ceramide levels and increases C22:0 , C24:0 , and C24:1 ceramide levels in mouse skeletal muscle. It increases fatty acid oxidation in mouse skeletal muscle and inhibits triglyceride synthesis and increases in white adipose mass in a model of high-fat diet-induced obesity but does not affect insulin resistance. | [Uses]
P053 is a potent, non-competitive and selective ceramide synthase 1 (CerS1) inhibitor wirh an IC50 of 0.5?μM. P053 acts as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle. Whole-body adiposity regulator[1]. | [in vivo]
P053 (5?mg/kg; administered daily by oral gavage; 7 days, in male C57BL6/J mice ) reduces C18 ceramide levels in skeletal muscle (SkM) [1].
Daily P053 administration to mice fed a high-fat diet (HFD) increases fatty acid oxidation in skeletal muscle and impedes increases in muscle triglycerides and adiposity, but does not protect against HFD-induced insulin resistance[1]. | Animal Model: | Male C57BL6/J mice[1] | | Dosage: | 5?mg/kg | | Administration: | Oral gavage; daily | | Result: | Reduced C18 ceramide levels in SkM by 31%, whereas 1?mg/kg/day had no effect. |
| [References]
1. Turner, N., Lim, X.Y., Toop, H.D., et al. A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism Nat. Commun. 9(1),3165(2018). |
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