| Identification | Back Directory | [Name]
LY-2562175 | [CAS]
1103500-20-4 | [Synonyms]
CS-2847
LY-2562175
1H-Indole-3-carboxylic acid, 6-[4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]-1-piperidinyl]-1-methyl- | [Molecular Formula]
C28H27Cl2N3O4 | [MDL Number]
MFCD30738721 | [MOL File]
1103500-20-4.mol | [Molecular Weight]
540.44 |
| Chemical Properties | Back Directory | [Boiling point ]
740.1±60.0 °C(Predicted) | [density ]
1.48±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 20 mg/ml; DMSO: 30 mg/ml; DMSO:PBS (pH 7.2) (1:3): 0.25 mg/ml | [form ]
A crystalline solid | [pka]
3.43±0.10(Predicted) | [color ]
White to light yellow |
| Hazard Information | Back Directory | [Description]
LY2562175 is a farnesoid X receptor (FXR) agonist (EC50 = 193 nM in a reporter assay). It is selective for FXR over the glucocorticoid, androgen, mineralocorticoid, and progesterone receptors in HEK293 cells overexpressing the human receptors (EC50s = >10 μM for all in a radioligand binding assay). LY2562175 increases the interaction between FXR and steroid receptor coactivator 1 (SRC-1) with an EC50 value of 121 nM in a cell-free assay. It reduces plasma triglyceride and total cholesterol levels in LDL receptor-null mice (ED50s = 3.4 and 2 mg/kg, respectively). LY2562175 also decreases plasma LDL and increases HDL levels in Zucker diabetic fatty (ZDF) rats when administered at doses of 3, 10, and 30 mg/kg for nine days. | [Uses]
LY2562175, is a potent and selective FXR agonist with an EC50 of 193 nM. | [in vivo]
LY2562175 causes a dose-dependent decrease in serum cholesterol and serum triglycerides. At a dose of 10 mg/kg, the decrease in cholesterol with LY2562175 is 80% below vehicle-treated animals, and the decrease in serum triglycerides is 76% from control group. The ED50 for serum cholesterol is determined to be 2 and 3.4 mg/kg for serum triglycerides. Treatment of female ZDF rats with LY2562175 results in a dose dependent lowering of plasma triglycerides in the fasted and nonfasted states. When administered as a fixed dose combination with BRL49653, LY2562175 further lowers fasted and nonfasted plasma triglycerides. FPLC fractionation of the lipoproteins reveals that LY2562175 treatment results in a reduction in vLDL-C and a dramatic increase in HDL-c in this animal model[1]. | [References]
[1] MICHAEL J. GENIN*. Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic Acid: A Novel FXR Agonist for the Treatment of Dyslipidemia[J]. Journal of Medicinal Chemistry, 2015, 58 24: 9768-9772. DOI: 10.1021/acs.jmedchem.5b01161 |
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