Peso molecular: 481,33 T0901317 es un agonista potente y selectivo para LXR y FXR, con EC50 de ~ 50 nM y 5 μM, respectivamente. \ N Actividad biológica
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Description
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T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively.
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Targets
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LXR [1]
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FXR [2]
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IC50
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50 nM(EC50)
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5 μM(EC50)
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In vitro
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T0901317 acts through LXR and in concert with its RXR heterodimerization partner induces the expression of the ABCA1 reverse cholesterol transporter. T0901317 upregulates expression of the ABCA1 gene associated with cholesterol efflux regulation and HDL metabolism.[1] T0901317 displays an EC50 of ~ 5 μM for activation of bile acid farnesoid X receptors (FXRs), 10-fold more potent than natural FXR ligand chenodeoxycholic acid. [2] T0901317, is also a high-affinity ligand for the xenobiotic receptor pregnane X receptor (PXR). T0901317 binds and activates PXR with the same nanomolar potency with which it stimulates LXR activity. T0901317 induces expression not only of LXR target genes, but also of PXR target genes in cells and animals, including the scavenger receptor CD36. [3] T0901317 decreases amyloid-β production in primary neurons in vitro. [4] T0901317 is found to directly bind to RORα and RORγ with high affinity (Ki = 132 and 51 nM, respectively), resulting in the modulation of the receptor's ability to interact with transcriptional cofactor proteins. T0901317 represses RORα/γ-dependent transactivation of ROR-responsive reporter genes and in HepG2 cells reduces recruitment of steroid receptor coactivator-2 by RORα at an endogenous ROR target gene (G6Pase). [5]
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In vivo
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T0901317 treatment of 11-week-old APP23 mice for 6 days shows a significant increase in ABCA1 expression and a decrease in the ratio of soluble APP (sAPP)β- to sAPPα-cleavage products. Most importantly, the treatment causes a statistically significant reduction in the levels of soluble Aβ40 and of Aβ42 in the brain these mice. [4]
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Features
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Protocolo (solo como referencia) 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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Referencias [1] Repa JJ, et al. Science, 2000, 289 (5484), 1524-1529. [2] Houck KA y col. Mol Genet Metab, 2004, 83 (1-2), 184-187. [3] Mitro N, et al. FEBS Lett, 2007, 581 (9), 1721-1726. [4] Koldamova RP, et al. J Biol Chem, 2005, 280 (6), 4079-4088. [5] Kumar N y col. Mol Pharmacol, 2010, 77 (2), 228-236. Información química
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Molecular Weight (MW)
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481.33
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Formula
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C17H12F9NO3S
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CAS No.
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293754-55-9
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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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96 mg/mL
(199.44 mM)
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Water
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<1 mg/mL
(
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Ethanol
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96 mg/mL
(199.44 mM)
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Chemical Name
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Benzenesulfonamide, N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-
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Calculadora de molaridad Calculadora de dilución Calculadora de peso molecular
Grupos de Producto : Otros > Inhibidor del receptor X del hígado
