.cp_wz tabla {borde superior: 1px sólido #ccc; borde izquierdo: 1px sólido #ccc; } .cp_wz table td {borde derecho: 1px sólido #ccc; borde inferior: 1px sólido #ccc; padding: 5px 0px 0px 5px;} .cp_wz table th {border-right: 1px solid #ccc; border-bottom: 1px solid #ccc; relleno: 5px 0px 0px 5px;} \ n Peso molecular: 618.51 GW3965 HCl es un agonista LXR potente y selectivo para hLXRα y hLXRβ con EC50 de 190 y 30 nM, respectivamente. \ n Actividad biológica
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Description
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GW3965 HCl is a potent, selective LXR agonist for hLXRα and hLXRβ with EC50 of 190 and 30 nM, respectively.
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Targets
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hLXRβ [1]
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LXRα/SRC1 LiSA [1]
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hLXRα [1]
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IC50
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30 nM(EC50)
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125 nM(EC50)
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190 nM(EC50)
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In vitro
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GW3965 recruits the steroid receptor coactivator 1 to human LXRα with EC50 of 125 nM in a cell-free ligand-sensing assay. [1] GW3965 shows a potent antagonistic activity against hLXRα and hLXRβ in cell-based assays with EC50 of 190 nM and 30 nM, respectively. Besides, GW3965 also sows excellent selectivity over other nuclear receptors. [1] In human islets, GW3965 (1 μM) reduces expression of selected pro-inflammatory cytokines including IL-8, monocyte chemotactic protein-1 and tissue factor. [4]
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In vivo
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In mice, GW3965 at a dose of 10 mg/kg upregulates ABCA1 expression 8-fold and raises circulating levels of HDL by 30% with Cmax of 12.7 μg/mL and t1/2 of 2 hours. [1] GW3965 (10mg/kg) induces expression of ABCA1 and ABCG1 and shows potent antiatherogenic activity in both LDLR−/− and apoE−/− mice. [2] In male sprague-dawley rats, GW3965 reduces Ang II-mediated increases in blood pressure and decreases vascular Ang II receptor gene expression. [3] In Glioblastoma mouse model, GW3965 results in inducible degrader of LDLR-mediated LDLR degradation, increased expression of the ABCA1 cholesterol efflux transporter, and thus potently promotes tumor cell death. [5]
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Features
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Protocolo (solo como referencia) Estudio con animales: [1]
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Animal Models
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C57BL/6 mice
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Formulation
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GW3965 is dissolved in 0.5% Methyl Cellulose.
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Dosages
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≤10 mg/kg
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Administration
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Administered via p.o.
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Conversión de diferentes modelos de animales basados en BSA (valor basado en datos del Borrador de Directrices de la FDA)
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Species
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Baboon
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Dog
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Monkey
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Rabbit
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Guinea pig
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Rat
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Hamster
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Mouse
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Weight (kg)
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12
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10
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3
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1.8
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0.4
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0.15
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0.08
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0.02
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Body Surface Area (m2)
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0.6
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0.5
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0.24
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0.15
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0.05
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0.025
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0.02
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0.007
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Km factor
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20
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20
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12
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12
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8
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6
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5
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3
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Animal A (mg/kg) = Animal B (mg/kg) multiplied by
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Animal B Km
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Animal A Km
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Por ejemplo, para modificar la dosis de resveratrol utilizada para un ratón (22,4 mg / kg) a una dosis basada en el BSA para una rata, multiplique 22,4 mg / kg por el factor Km para un ratón y luego divida por el factor Km para una rata. Este cálculo da como resultado una dosis equivalente para ratas de resveratrol de 11,2 mg / kg.
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Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×
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mouse Km(3)
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= 11.2 mg/kg
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rat Km(6)
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1 Referencias [1] Collins JL, et al. J Med Chem. 2002, 45 (10), 1963-1966. [2] Joseph SB y col. Proc Natl Acad Sci US A. 2002, 99 (11), 7604-7609. [3] Leik CE, et al. Br J Pharmacol. 2007, 151 (4), 450-456. [4] Scholz H, et al. Diabetologia. 2009, 52 (7), 1352-1362. [5] Guo D y col. Cancer Discov. 2011, 1 (5), 442-456. Información química
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Molecular Weight (MW)
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618.51
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Formula
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C33H31ClF3NO3.HCl
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CAS No.
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405911-17-3
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Storage
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3 years -20℃Powder
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6 months-80℃in solvent (DMSO, water, etc.)
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Synonyms
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Solubility (25°C) *
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In vitro
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DMSO
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124 mg/mL
(200.48 mM)
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Water
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<1 mg/mL
(
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Ethanol
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<1 mg/mL
(
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Chemical Name
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2-(3-(3-((2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)amino)propoxy)phenyl)acetic acid hydrochloride
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
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Stock Solution (1ml DMSO)
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1mM
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10mM
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20mM
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30mM
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Mass(mg)
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0.61851
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6.1851
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12.3702
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18.5553
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Grupos de Producto : Otros > Inhibidor del receptor X del hígado
