Obeticholic Acid (INT-747) FXR agoniste

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Contrôle qualité

Lot : Pureté : 99.77%

99.77

Cibles apparentées	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Autre FXR Inhibiteurs	GW4064 Guggulsterone E&Z Turofexorate Isopropyl (XL335) fexaramine Tropifexor (LJN452) Cilofexor (GS-9674) BAR502 Nidufexor (LMB-763) LY2562175 Vonafexor (EYP001)

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Concentration	Temps dincubation	Description de lactivité	PMID
insect cells	Function assay		1 hr	Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assay, EC50 = 0.01 μM.	29148806
HEK293T	Function assay		24 hrs	Agonist activity at human FXR expressed in HEK293T cells assessed as BSEP promoter driven cellular transcriptional activity after 24 hrs by luciferase reporter gene assay, EC50 = 0.042 μM.	29148806
COS1	Function assay			Agonist activity at FXR expressed in COS1 cells by cell-based bioluminescence assay, EC50 = 0.099 μM.	20014870
HeLa	Function assay		24 hrs	Agonist activity at human full length FXR expressed in HeLa cells cotransfected with pSG5-human RXR after 24 hrs by Dual-Glo luciferase reporter gene assay, EC50 = 0.16 μM.	25934227
HeLa	Function assay			Agonist activity at human FXR expressed in human HeLa cells assessed as receptor activation by BSEP promoter-driven firefly luciferase reporter gene assay, EC50 = 0.16 μM.	25255039
insect cells	Function assay		1 hr	Agonist activity at recombinant human GST-tagged FXR LBD (193 to 472 residues) expressed in baculovirus-infected insect cells assessed as recruitment of biotinylated SRC1 peptide measured after 1 hr by Alphascreen assay, EC50 = 0.18 μM.	29259742
COS1	Function assay		5 hrs	Agonist activity at human FXR expressed in COS1 cells after 5 hrs by CRE-driven luciferase reporter gene assay, EC50 = 0.361 μM.	17685603
CHO	Function assay		5 hrs	Agonist activity at human TGR5 expressed in CHO cells after 5 hrs by CRE-driven luciferase reporter gene assay, EC50 = 0.755 μM.	17685603
HEK293	Function assay		1 hr	Agonist activity at human TGR5 expressed in HEK293 cells assessed as increase in intracellular cAMP level after 1 hr by TR-FRET assay, EC50 = 0.84 μM.	29259742
NCI-H716	Function assay			Agonist activity at human TGR5 receptor expressed in NCI-H716 cells assessed as intracellular cAMP level by TR-FRET assay, EC50 = 20 μM.	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated SHP mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated SHP mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated BSEP mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated Ostbeta mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated down-regulation of Cyp7A1 mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Induction of FXR-mediated down-regulation of Cyp7A1 mRNA expression in human HepG2 cells at 20 uM by RT-PCR	21459580
HepG2	Function assay	20 uM		Agonist activity at human FXR expressed in HepG2 cells assessed as renilla luciferase activity at 20 uM by luciferase based transactivation assay	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated BSEP mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	1 uM		Induction of FXR-mediated Ostbeta mRNA expression in human HepG2 cells at 1 uM by RT-PCR	21459580
HepG2	Function assay	10 uM		Transactivation of human FXR transfected in human HepG2 cells at 10 uM by beta-galactosidase reporter gene assay	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of OST-alpha mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
GLUTag	Function assay			Agonist activity at GP-BAR1 in mouse GLUTag cells assessed as increase in intracellular cAMP level	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of SHP mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
HepG2	Function assay	10 uM	18 hrs	Agonist activity at FXR in human HepG2 cells assessed as upregulation of BESP mRNA expression at 10 uM after 18 hrs by RT-PCR analysis	24387325
GLUTag	Function assay			Agonist activity at GP-BAR1 in mouse GLUTag cells assessed as increase in GLP-1 release	24387325
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Informations chimiques, stockage et stabilité

Poids moléculaire	420.63	Formule	C₂₆H₄₄O₄	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	459789-99-2	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	6-ECDCA, 6-Ethylchenodeoxycholic acid			Smiles	CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O

Solubilité

In vitro
Lot:

DMSO : 84 mg/mL (199.7 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 84 mg/mL

Water : Insoluble

Calculateur de molarité

Masse	Concentration	Volume	Poids moléculaire
=	×	×

Calculateur de dilution Calculateur de poids moléculaire

In vivo Lot:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe de vente pour des tests personnalisés.	4.250mg/ml (10.10mM)	Taking the 1 mL working solution as an example, add 50 μL of 85 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe de vente pour des tests personnalisés.	1.100mg/ml (2.62mM)	Taking the 1 mL working solution as an example, add 50 μL of 22 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Calculateur de formulation in vivo (Solution claire)

Étape 1 : Entrez les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant lexpérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre danimaux :

Étape 2 : Entrez la formulation in vivo (Ceci nest que le calculateur, pas la formulation. Veuillez nous contacter dabord sil ny a pas de formulation in vivo dans la section Solubilité.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Résultats du calcul :

Concentration de travail : mg/ml;

Méthode de préparation du liquide maître DMSO : mg médicament prédissous dans μL DMSO ( Concentration du liquide maître mg/mL, Veuillez nous contacter dabord si la concentration dépasse la solubilité du DMSO du lot de médicament. )

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuiteμL PEG300, mélanger et clarifier, ajouter ensuiteμL Tween 80, mélanger et clarifier, ajouter ensuite μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, ajouter ensuite μL Huile de maïs, mélanger et clarifier.

Remarque : 1. Assurez-vous que le liquide est clair avant dajouter le solvant suivant.
2. Assurez-vous dajouter le(s) solvant(s) dans lordre. Vous devez vous assurer que la solution obtenue lors de lajout précédent est une solution claire avant de procéder à lajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie peuvent être utilisées pour faciliter la dissolution.

Mécanisme daction

Targets/IC₅₀/Ki	FXR 99 nM(EC50)
In vitro	Dans les cellules HuH7, Obeticholic Acid (INT-747) agit comme un puissant agoniste du FXR avec une EC50 de 85 nM.
Kinase Assay	Puissance de liaison de Obeticholic Acid au FXR
Kinase Assay	Obeticholic Acid (INT-747) a été testé dans un essai de détection de ligand sans cellule établi, qui mesure le recrutement ligand-dépendant d'un peptide SRC1 au FXR par transfert d'énergie de résonance par fluorescence.
In vivo	Dans le modèle de cholestase chez le rat, Obeticholic Acid (INT-747) favorise le flux biliaire et protège les hépatocytes contre la nécrose aiguë causée par le LCA. Ce composé (p.o.) améliore la protéinurie, atténue les modifications structurelles rénales et module l'inflammation rénale et le stress oxydatif chez les souris DBA nourries avec un régime WD. Chez les rats intoxiqués au thioacétamide (TAA) et ligaturés au canal biliaire (BDL), il (30 mg/kg p.o.) réactive la voie de signalisation en aval du FXR et diminue la pression portale en abaissant l'IHVR totale sans hypotension systémique délétère.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/12166927/ [2] https://pubmed.ncbi.nlm.nih.gov/19776172/ [3] https://pubmed.ncbi.nlm.nih.gov/24259407/

Applications

Méthodes	Biomarqueurs	Images	PMID
Western blot	p-IRE1α XBP1s		29377207

Informations sur lessai clinique

(données de https://clinicaltrials.gov, mis à jour le 2024-05-22)

Numéro NCT	Recrutement	Conditions	Sponsor/Collaborateurs	Date de début	Phases
NCT05740631	Recruiting	Healthy	Universitaire Ziekenhuizen KU Leuven\|Intercept Pharmaceuticals	August 22 2022	Not Applicable
NCT02633956	Completed	Nonalcoholic Steatohepatitis	Intercept Pharmaceuticals	December 4 2015	Phase 2
NCT02548351	Terminated	Non Alcoholic Steatohepatitis (NASH)	Intercept Pharmaceuticals	September 22 2015	Phase 3

Support technique

Instructions de manipulation

Tel: +1-832-582-8158 Ext:3

Si vous avez dautres questions, veuillez laisser un message.

Questions fréquemment posées

Question 1:
What formulation can we use to dissolve it for mice in vivo study?

Réponse :
You can use the vehicle of: 1% wt/vol methyl-cellulose as indicated in this paper, http://www.sciencedirect.com/science/article/pii/S0925443911000883 "daily oral gavage with 5 mg/kg/day of this compound or vehicle (1% wt/vol methyl-cellulose) from 3 days prior to induction of colitis"

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Structure chimique

Poids moléculaire: 420.63