Obeticholic Acid (INT-747) FXR agonista

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Control de calidad

Lote: Pureza: 99.77%

99.77

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

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Concentración	Tiempo de incubación	Descripción de la actividad	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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Información química, almacenamiento y estabilidad

Peso molecular	420.63	Fórmula	C₂₆H₄₄O₄	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	459789-99-2	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	6-ECDCA, 6-Ethylchenodeoxycholic acid			Smiles	CCC1C2CC(CCC2(C3CCC4(C(C3C1O)CCC4C(C)CCC(=O)O)C)C)O

Solubilidad

In vitro
Lote:

DMSO : 84 mg/mL (199.7 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 84 mg/mL

Water : Insoluble

Calculadora de Molaridad

Masa	Concentración	Volumen	Peso molecular
=	×	×

Calculadora de Dilución Calculadora de Peso Molecular

In vivo Lote:
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 Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	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 Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	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.

Calculadora de formulación in vivo (Solución clara)

Paso 1: Introduzca la información a continuación (Recomendado: Un animal adicional para tener en cuenta la pérdida durante el experimento)

Dosis: mg/kg Peso promedio de los animales: g Volumen de dosificación por animal:μL Número de animales:

Paso 2: Introduzca la formulación in vivo (Esto es solo la calculadora, no la formulación. Por favor, contáctenos primero si no hay una formulación in vivo en la sección de Solubilidad.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Resultados del cálculo:

Concentración de trabajo: mg/ml;

Método para preparar el líquido maestro de DMSO: mg fármaco predissuelto en μL DMSO ( Concentración del líquido maestro mg/mL, Por favor, contáctenos primero si la concentración excede la solubilidad del DMSO del lote del fármaco. )

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadirμL PEG300, mezclar y clarificar, luego añadirμL Tween 80, mezclar y clarificar, luego añadir μL ddH₂O, mezclar y clarificar.

Método para preparar la formulación in vivo: Tomar μL DMSO líquido maestro, luego añadir μL Aceite de maíz, mezclar y clarificar.

Nota: 1. Por favor, asegúrese de que el líquido esté claro antes de añadir el siguiente disolvente.
2. Asegúrese de añadir el (los) disolvente(s) en orden. Debe asegurarse de que la solución obtenida, en la adición anterior, sea una solución clara antes de proceder a añadir el siguiente disolvente. Se pueden utilizar métodos físicos como el vórtice, el ultrasonido o el baño de agua caliente para ayudar a la disolución.

Mecanismo de acción

Targets/IC₅₀/Ki	FXR 99 nM(EC50)
In vitro	En células HuH7, Obeticholic Acid (INT-747) actúa como un potente agonista de FXR con una EC50 de 85 nM.
Ensayo de quinasa	Potencia de unión de Obeticholic Acid a FXR
Ensayo de quinasa	Obeticholic Acid (INT-747) se probó en un ensayo establecido de detección de ligandos sin células, que mide el reclutamiento dependiente del ligando de un péptido SRC1 a FXR mediante transferencia de energía de resonancia de fluorescencia.
In vivo	En el modelo de colestasis en ratas, Obeticholic Acid (INT-747) promueve el flujo biliar y protege los hepatocitos contra la necrosis aguda causada por LCA. Este compuesto (p.o.) mejora la proteinuria, atenúa los cambios estructurales renales y modula la inflamación renal y el estrés oxidativo en ratones DBA alimentados con WD. En ratas intoxicadas con tioacetamida (TAA) y con ligadura del conducto biliar (BDL), (30 mg/kg p.o.) reactiva la vía de señalización descendente de FXR y disminuye la presión portal al reducir el IHVR total sin hipotensión sistémica deletérea.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/12166927/ [2] https://pubmed.ncbi.nlm.nih.gov/19776172/ [3] https://pubmed.ncbi.nlm.nih.gov/24259407/

Aplicaciones

Métodos	Biomarcadores	Imágenes	PMID
Western blot	p-IRE1α XBP1s		29377207

Información del ensayo clínico

(datos de https://clinicaltrials.gov, actualizado el 2024-05-22)

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
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

Soporte técnico

Instrucciones de manipulación

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Preguntas frecuentes

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

Respuesta:
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"

C1=C0/X	C1:	LOG(C1):
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C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Estructura química

Peso molecular: 420.63