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Molekulargewicht: 420,63 Obeticholic Acid ist ein potenter und selektiver Farnesoid-X-Rezeptor (FXR)-Agonist mit EC50 von 99 nM. Phase 3.
Biologische Aktivität
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Description
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Obeticholic Acid is a potent and selective farnesoid X receptor (FXR) agonist with EC50 of 99 nM. Phase 3.
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Targets
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FXR [1]
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IC50
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99 nM(EC50)
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In vitro
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In HuH7 cells, Obeticholic Acid acts as a potent FXR agonist with EC50 of 85 nM.
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In vivo
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In rat cholestasis model, Obeticholic Aci promotes bile flow, and protects hepatocytes against acute necrosis caused by LCA. Obeticholic Acid (p.o.) improves proteinuria, ameliorates renal structural changes, and modulates renal inflammation and oxidative stress in WD-fed DBA mice. In thioacetamide (TAA)-intoxicated and bile-duct-ligated (BDL) rats, Obeticholic Acid (30 mg/kg p.o.) reactivates the FXR downstream signaling pathway and decreases portal pressure by lowering total IHVR without deleterious systemic hypotension.
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Features
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Protokoll (nur als Referenz) Kinase-Assay: [1]
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Binding Potency of Obeticholic Acid to FXR
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The compound is tested in an established cell-free ligand sensing assay, which measures the ligand-dependent recruitment of an SRC1 peptide to FXR by fluorescence resonance energy transfer.
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Tierstudie: [1]
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Animal Models
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Rat cholestasis model
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Formulation
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7 μmol/kg/min
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Dosages
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Saline
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Administration
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Infused at the right jugular vein using PE-50 polyethylene tubing
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Umrechnung verschiedener Modelltiere basierend auf BSA (Wert basierend auf Daten aus FDA Draft Guidelines)
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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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Um beispielsweise die Resveratrol-Dosis für eine Maus (22,4 mg/kg) auf eine Dosis basierend auf dem BSA für eine Ratte zu ändern, multiplizieren Sie 22,4 mg/kg mit dem Km-Faktor für eine Maus und dividieren Sie dann durch den Km-Faktor für eine Ratte. Diese Berechnung ergibt eine Ratten-Äquivalentdosis für Resveratrol von 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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Chemische Informationen
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Molecular Weight (MW)
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420.63
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Formula
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C26H44O4
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CAS No.
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459789-99-2
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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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INT-747, 6-ECDCA
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Solubility (25°C) *
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In vitro
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DMSO
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84 mg/mL
(199.7 mM)
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Water
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<1 mg/mL
(
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Ethanol
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84 mg/mL
(199.7 mM)
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Chemical Name
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(3α,5β,6α,7α)-6-ethyl-3,7-dihydroxy-cholan-24-oic acid
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Molaritätsrechner Verdünnungsrechner Molekulargewichtsrechner
Produktgruppe : Andere > FXR-Inhibitor
