Name: Dapagliflozin (BMS-512148)
Brand: Selleck Chemicals
SKU: S1548
Rating: 5 (44 reviews)

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Lote: Pureza: 99.99%

99.99

Dianas relacionadas	CXCR Hedgehog/Smoothened PKA Adrenergic Receptor AChR 5-HT Receptor Histamine Receptor Dopamine Receptor Ras KRas
Otros SGLT Inhibidores	Sotagliflozin (LX4211) Phlorizin Phloretin (RJC 02792) Tofogliflozin(CSG 452) Ipragliflozin (ASP1941) KGA-2727 Mizagliflozin (KWA 0711, DSP-3235 free base) Ipragliflozin L-Proline Bexagliflozin (EGT1442) Swertisin

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
CHO cells	Function assay	2 h	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50=0.00049 μM	20434909
CHOK1 cells	Function assay	3 h	Inhibition of human SGLT2 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50=0.001 μM	24842618
HEK293.ETN cells	Function assay	1.5 h	Inhibition of human SGLT2 transfected in HEK293.ETN cells assessed as AMG uptake after 1.5 hrs by scintillation counting, IC50=0.0067 μM	19896374
COS-7 cells	Function assay	2 h	Inhibition of human SGLT1 transfected in COS-7 cells assessed as AMG uptake after 2 hrs by scintillation counting, IC50=0.89 μM	19896374
CHO	Function assay		Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 0.0011 μM.	18260618
CHO	Function assay		Inhibition of rat SGLT2 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 0.003 μM.	18260618
CHO	Function assay		Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of [14C]AMG accumulation, EC50 = 1.39 μM.	18260618
HEK293.ETN	Function assay		Inhibition of human SGLT2 expressed in HEK293.ETN cells assessed as methyl-alpha-D-[U-14C]glucopyranoside uptake by scintillation counting, IC50 = 0.0067 μM.	19700318
COS7	Function assay		Inhibition of human SGLT1 expressed in african green monkey COS7 cells assessed as methyl-alpha-D-[U-14C]glucopyranoside uptake by scintillation counting, IC50 = 0.885 μM.	19700318
HEK293	Function assay		Inhibition of human SGLT1 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methylglucopyranoside uptake, IC50 = 0.81 μM.	19785435
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent methyl-alpha-D-[U-14C]glucopyranoside uptake after 2 hrs, IC50 = 0.0014 μM.	20149653
CHO	Function assay	2 hrs	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of sodium-dependent methyl-alpha-D-[U-14C]glucopyranoside uptake after 2 hrs, IC50 = 1.2 μM.	20149653
CHO	Function assay		Inhibition of human recombinant SGLT2 expressed in CHO cells by liquid scintillation counting, IC50 = 0.00049 μM.	20181486
HEK293	Function assay	1.5 hrs	Inhibition of human SGLT2 expressed in HEK293 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 1.5 hrs by liquid scintillation counting, IC50 = 0.0067 μM.	20576578
COS7	Function assay	2 hrs	Inhibition of human SGLT1 expressed in african green monkey COS7 cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.89 μM.	20576578
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, EC50 = 0.003 μM.	21128592
CHO	Function assay	2 hrs	Inhibition of human SGLT1 expressed in CHO cells assessed as sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, EC50 = 0.4285 μM.	21128592
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	21193308
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.004 μM.	21398124
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting in presence of 100% plasma, IC50 = 0.022 μM.	21398124
CHO	Function assay	60 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.37 μM.	21398124
CHO	Function assay	60 mins	Inhibition of SGLT6 expressed in CHO cells assessed as inhibition of [14C]-alpha-methyl-D-glucopyranoside transport after 60 mins by scintillation counting, IC50 = 0.38 μM.	21398124
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counter, IC50 = 0.00049 μM.	21514014
CHO	Function assay	60 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of [14C]-Glucose uptake using [14C]-methyl glucopyranoside after 60 mins by microbeta plate counting, IC50 = 0.003 μM.	21565497
CHO	Function assay		Inhibition of human SGLT2 expressed in CHO cells using methyl-alpha-D-glucopyranoside by liquid scintillation counting, IC50 = 0.00135 μM.	21592794
COS7	Function assay	2 hrs	Inhibition of human SGLT2 expressed in african green monkey COS7 cells assessed as inhibition of [14C]-methyl-alpha-D-glucopyranoside uptake after 2 hrs by scintillation counting in presence of 25 % human plasma, IC50 = 0.0032 μM.	21737266
293	Function assay	1.5 hrs	Inhibition of human SGLT1 expressed in human 293 cells assessed as inhibition of [14C]-methyl-alpha-D-glucopyranoside uptake after 1.5 hrs by scintillation counting in presence of 25 % human plasma, IC50 = 3.1 μM.	21737266
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as reduction of [14C]-labeled AMG after 2 hrs by liquid scintillation counting, IC50 = 0.00135 μM.	21868239
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	21906953
CHO-K1	Function assay		Inhibition of human SGLT2 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.0013 μM.	22652255
CHO-K1	Function assay		Inhibition of human SGLT1 expressed in CHO-K1 cells by [14C]AMG uptake assay, IC50 = 0.8 μM.	22652255
CHO-K1	Function assay	120 mins	Inhibition of human SGLT2 expressed in CHO-K1 cells incubated for 120 mins at 37 degC by [14C]-AMG uptake assay, EC50 = 0.0024 μM.	22818040
CHO-K1	Function assay	120 mins	Inhibition of human SGLT1 expressed in CHO-K1 cells incubated for 120 mins at 37 degC by [14C]-AMG uptake assay, EC50 = 0.593 μM.	22818040
CHO	Function assay	45 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]methyl-alpha-D-glucopyranoside uptake after 45 mins, IC50 = 0.0013 μM.	22889351
CHO	Function assay	45 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]methyl-alpha-D-glucopyranoside uptake after 45 mins, IC50 = 0.8 μM.	22889351
CHOK1	Function assay	3 hrs	Inhibition of human SGLT1 expressed in CHOK1 cells assessed as inhibition of [14C]-AMG uptake after 3 hrs by microbeta scintillation counting analysis, IC50 = 0.891 μM.	24842618
CHO	Function assay	2 hrs	Inhibition of human SGLT2 expressed in CHO cells assessed as [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by liquid scintillation counting, IC50 = 0.00049 μM.	24900297
CHO	Function assay	2 hrs	Competitive inhibition of full-length human SGLT2 expressed in CHO cells assessed as inhibition of sodium-dependent [14C]-alpha-methyl-D-glucopyranoside uptake after 2 hrs by scintillation counting, IC50 = 0.005 μM.	25650254
CHO	Function assay	120 mins	Inhibition of human SGLT2 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.0015 μM.	28447791
CHO	Function assay	120 mins	Inhibition of human SGLT1 expressed in CHO cells assessed as decrease in uptake of [14C]AMG after 120 mins by TopCount method, IC50 = 0.629 μM.	28447791
CHO	Function assay	1 hr	Inhibition of human SGLT2 expressed in CHO cells assessed as reduction in [14C]AMG uptake after 1 hr by microbeta counting method, EC50 = 0.002 μM.	29216560
CHO	Function assay	1 hr	Inhibition of human SGLT1 expressed in CHO cells assessed as reduction in [14C]AMG uptake after 1 hr by microbeta counting method, EC50 = 0.86 μM.	29216560
CHO	Function assay	1 hr	Inhibition of full-length human SGLT2 expressed in CHO cells assessed as decrease in [14C]-methyl alpha-D-glucopyranoside uptake after 1 hr by liquid scintillation counting method, IC50 = 0.00105 μM.	29764742
HEK293	Function assay	10 mins	Inhibition of human SGLT2 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by liquid scintillation counting method, IC50 = 0.0014 μM.	29954682
HEK293	Function assay	10 mins	Inhibition of human SGLT1 expressed in HEK293 cells assessed as decrease in [14C]-AMG uptake preincubated for 10 mins followed by [14C]-AMG addition and measured after 2 hrs by liquid scintillation counting method, IC50 = 1.83 μM.	29954682
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Información química, almacenamiento y estabilidad

Peso molecular	408.87	Fórmula	C₂₁H₂₅ClO₆	Almacenamiento (Desde la fecha de recepción)	3 years -20°C powder (seal)
Nº CAS	461432-26-8	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	BMS-512148			Smiles	CCOC1=CC=C(C=C1)CC2=C(C=CC(=C2)C3C(C(C(C(O3)CO)O)O)O)Cl

Solubilidad

In vitro
Lote:

DMSO : 100 mg/mL (244.57 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 100 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.
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.
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.	4.100mg/ml (10.03mM)	Taking the 1 mL working solution as an example, add 50 μL 82 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

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

Características	More potent stimulator of glucosuria than other SGLT2 inhibitors.
Targets/IC₅₀/Ki	hSGLT2 (CHO cells) 1.1 nM(EC50)
In vitro	Dapagliflozin no es sensible a hSGLT1 con una IC50 1200 veces mayor. Este compuesto es 32 veces más potente que la florizina contra hSGLT2, pero 4 veces menos potente que la florizina contra hSGLT1. Es altamente selectivo frente a los transportadores GLUT y muestra una inhibición del 8-9 % en un tampón sin proteínas a 20 μM y prácticamente ninguna inhibición en presencia de 4 % de albúmina sérica bovina. Este compuesto químico tiene buena permeabilidad a través de las membranas de las células Caco-2 y es un sustrato de la P-glicoproteína (P-gp), pero no un inhibidor significativo de la P-gp. Es estable en suero de rata, perro, mono y humano a 10 μM. No muestra respuestas inhibitorias ni inducción a las enzimas P450 humanas. Las vías metabólicas in vitro de este compuesto son la glucuronidación, la hidroxilación y la O-desetilación.
Ensayo de quinasa	Ensayos de unión a SGLT
Ensayo de quinasa	Se utilizan células de ovario de hámster chino (CHO) que expresan de forma estable SGLT2 humano (hSGLT2) y SGLT1 humano (hSGLT1) para el desarrollo de ensayos de transporte utilizando el sustrato selectivo de SGLT α-metil-D-glucopiranósido (AMG). Se ensaya la capacidad de Dapagliflozin para inhibir la captación de [¹⁴C]AMG en un tampón libre de proteínas durante un período de incubación de 2 horas. La curva de respuesta se ajusta a un modelo empírico de cuatro parámetros para determinar la concentración del inhibidor a la respuesta semimáxima, reportada como EC50. Se utiliza un tampón libre de proteínas para simular las condiciones de baja concentración de proteínas del filtrado glomerular, que baña los objetivos SGLT en la superficie luminal del túbulo proximal en el riñón.
In vivo	Dapagliflozin reduce los niveles de glucosa en sangre en un 55 % después de una dosis oral de 0,1 mg/kg en ratas hiperglucémicas con estreptozotocina (STZ), lo que se debe en parte a la estabilidad metabólica conferida por el enlace C-glucósido. Este compuesto presenta un perfil favorable de absorción, distribución, metabolismo y excreción (ADME) y es biodisponible por vía oral. Este compuesto químico (1 mg/kg) causa una glucosuria significativa dependiente de la dosis y un aumento en el volumen de orina en ratas normales durante 24 horas después de la dosis. Induce un aumento en la excreción de glucosa y volumen de orina a las 6 horas después de la dosis en ratas Zucker diabéticas obesas (ZDF). Este agente reduce los niveles de glucosa en ayunas y postprandiales en ratas ZDF incluso después de 2 semanas de tratamiento, sin ningún marcador de toxicidad renal o hepática. Reduce significativamente el desarrollo de hiperglucemia, con niveles de glucosa en sangre más bajos. Este compuesto podría mejorar la sensibilidad a la insulina, reducir la masa de células β y el desarrollo de una función pancreática deteriorada.
Referencias	[1] https://pubmed.ncbi.nlm.nih.gov/18260618/ [2] https://pubmed.ncbi.nlm.nih.gov/18356408/ [3] https://pubmed.ncbi.nlm.nih.gov/19996149/ [4] https://pubmed.ncbi.nlm.nih.gov/20880347/ [5] https://pubmed.ncbi.nlm.nih.gov/34836340/

Aplicaciones

Métodos	Biomarcadores	PMID
Western blot	p-elf2α / t-elf2α / tubulin-α HIF-1α / PHD2 / tubulin DDR1 HIF-1α / p-AMPK / AMPK / p-ERK / ERK / β-actin Bax / Bcl2 / PARP / β-actin	31285506
Growth inhibition assay	Tumor volume	28763435
IHC	HE staining / SGLT2 mice kidney sections TUNEL-positive cells HIF1 TUNEL-positive cells	28763435
Immunofluorescence	podocytes PECAM-1 / α-SMA EdU F-actin Metabolic switch in diabetic kidneys	30089717

Información del ensayo clínico

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

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT06012266	Not yet recruiting	Heart Failure	Centre Hospitalier Universitaire Vaudois\|Great Ormond Street Hospital for Children NHS Foundation Trust\|University College London	August 2024	Phase 2
NCT06336330	Recruiting	Heart Diseases\|Cardiovascular Diseases\|Heart Failure	AstraZeneca	April 25 2024	--
NCT04887935	Not yet recruiting	Prostate Cancer\|Cancer of Prostate	Washington University School of Medicine\|The Foundation for Barnes-Jewish Hospital	April 30 2024	Phase 1
NCT06398977	Recruiting	Peritoneal Dialysis Complication\|Renal Function Aggravated\|Sodium-glucose Co-transporter-2 Inhibitors	Sichuan Academy of Medical Sciences	March 11 2024	Not Applicable

Soporte técnico

Instrucciones de manipulación

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

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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):

Dapagliflozin (BMS-512148) inhibidor de SGLT2

Estructura química

Peso molecular: 408.87