Name: Avagacestat (BMS-708163)
Brand: Selleck Chemicals
SKU: S1262
Rating: 5 (22 reviews)

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Control de calidad

Lote: Pureza: 99.63%

99.63

Dianas relacionadas	HDAC Caspase Proteasome MMP HCV Protease Cysteine Protease DPP Tyrosinase HIV Protease Serine Protease
Otros Secretase Inhibidores	DAPT RO4929097 (RG-4733) LY411575 Nirogacestat (PF-03084014) Dibenzazepine (YO-01027) Semagacestat (LY450139) MK-0752 MDL-28170 L-685,458 NGP 555

Cultivo celular, tratamiento y concentración de trabajo

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using APP as substrate after 2 hrs by ELISA, IC50=0.13 nM
human H4 cells	Function assay		Inhibition of gamma secretase-mediated amyloid beta42 production in human H4 cells expressing human APP swedish mutant, IC50=0.225 μM
HEK293 cells	Function assay		Inhibition of gamma-secretase in HEK293 cells after overnight incubation by Western blotting analysis, IC50=1.2 nM
CHO cells	Function assay		Inhibition of gamma-secretase in CHO cells assessed expressing APPSw assessed as inhibition of amyloid beta(1 to x) secretion after overnight incubation by ELISA, ED50=1.2 nM
human IMR32 cell	Function assay	2 h	Inhibition of gamma-secretase in human IMR32 cell membrane using Notch as substrate after 2 hrs by ELISA, IC50=1.5 nM
human 786-0 cell	Growth inhibition assay		Inhibition of human 786-0 cell growth in a cell viability assay, IC50=0.32173 μM
human NCI-H810 cell	Growth inhibition assay		Inhibition of human NCI-H810 cell growth in a cell viability assay, IC50=0.42598 μM
human IGR-1 cell	Growth inhibition assay		Inhibition of human IGR-1 cell growth in a cell viability assay, IC50=1.04778 μM
human SK-MEL-3 cell	Growth inhibition assay		Inhibition of human SK-MEL-3 cell growth in a cell viability assay, IC50=1.49922 μM
human HT-1080 cell	Growth inhibition assay		Inhibition of human HT-1080 cell growth in a cell viability assay, IC50=2.48764 μM
human NCI-H23 cell	Growth inhibition assay		Inhibition of human NCI-H23 cell growth in a cell viability assay, IC50=3.9322 μM
human Calu-6 cell	Growth inhibition assay		Inhibition of human Calu-6 cell growth in a cell viability assay, IC50=4.96014 μM
human CAPAN-1 cell	Growth inhibition assay		Inhibition of human CAPAN-1 cell growth in a cell viability assay, IC50=5.17886 μM
human COLO-668 cell	Growth inhibition assay		Inhibition of human COLO-668 cell growth in a cell viability assay, IC50=5.40221 μM
human TE-6 cell	Growth inhibition assay		Inhibition of human TE-6 cell growth in a cell viability assay, IC50=6.19082 μM
human LCLC-97TM1 cell	Growth inhibition assay		Inhibition of human LCLC-97TM1 cell growth in a cell viability assay, IC50=10.0886 μM
human CAS-1 cell	Growth inhibition assay		Inhibition of human CAS-1 cell growth in a cell viability assay, IC50=13.671 μM
human RPMI-2650 cell	Growth inhibition assay		Inhibition of human RPMI-2650 cell growth in a cell viability assay, IC50=13.8124 μM
human MDA-MB-157 cell	Growth inhibition assay		Inhibition of human MDA-MB-157 cell growth in a cell viability assay, IC50=14.2431 μM
human KINGS-1 cell	Growth inhibition assay		Inhibition of human KINGS-1 cell growth in a cell viability assay, IC50=14.3762 μM
human BB49-HNC cell	Growth inhibition assay		Inhibition of human BB49-HNC cell growth in a cell viability assay, IC50=14.4138 μM
human SK-UT-1 cell	Growth inhibition assay		Inhibition of human SK-UT-1 cell growth in a cell viability assay, IC50=14.6882 μM
human EW-11 cell	Growth inhibition assay		Inhibition of human EW-11 cell growth in a cell viability assay, IC50=14.8832 μM
human D-502MG cell	Growth inhibition assay		Inhibition of human D-502MG cell growth in a cell viability assay, IC50=14.9034 μM
human MMAC-SF cell	Growth inhibition assay		Inhibition of human MMAC-SF cell growth in a cell viability assay, IC50=15.0833 μM
human NCI-H1648 cell	Growth inhibition assay		Inhibition of human NCI-H1648 cell growth in a cell viability assay, IC50=15.778 μM
human NCI-H292 cell	Growth inhibition assay		Inhibition of human NCI-H292 cell growth in a cell viability assay, IC50=15.8806 μM
human NMC-G1 cell	Growth inhibition assay		Inhibition of human NMC-G1 cell growth in a cell viability assay, IC50=16.6293 μM
human SAS cell	Growth inhibition assay		Inhibition of human SAS cell growth in a cell viability assay, IC50=17.7812 μM
human HCT-116 cell	Growth inhibition assay		Inhibition of human HCT-116 cell growth in a cell viability assay, IC50=18.7965 μM
human SBC-5 cell	Growth inhibition assay		Inhibition of human SBC-5 cell growth in a cell viability assay, IC50=19.03 μM
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Información química, almacenamiento y estabilidad

Peso molecular	520.88	Fórmula	C₂₀H₁₇ClF₄N₄O₄S	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1146699-66-2	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	N/A			Smiles	C1=CC(=CC=C1S(=O)(=O)N(CC2=C(C=C(C=C2)C3=NOC=N3)F)C(CCC(F)(F)F)C(=O)N)Cl

Solubilidad

In vitro
Lote:

DMSO : 104 mg/mL (199.66 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Water : Insoluble

Ethanol : 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.	5.000mg/ml (9.60mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 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.	1.650mg/ml (3.17mM)	Taking the 1 mL working solution as an example, add 50 μL of 33 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.

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	Appears to be more “notch sparing” than semagacestat (LY450139).
Targets/IC₅₀/Ki	Aβ42 (in H4-8Sw cells) 0.27 nM Aβ40 (in H4-8Sw cells) 0.3 nM
In vitro	Avagacestat (BMS-708163) exhibe una selectividad más débil para la inhibición del procesamiento de Notch con un valor de IC50 de 193 veces.
In vivo	Avagacestat (BMS-708163) reduce significativamente los niveles de Aβ40 durante períodos sostenidos en el cerebro, plasma y líquido cefalorraquídeo en ratas y perros después de la administración oral. No tiene efectos limitantes de la dosis en perros (3 mg/kg durante 6 meses), con una alta relación cerebro/plasma (2,4).
Referencias	[1] http://pubs.acs.org/doi/abs/10.1021/ml1000239

Información del ensayo clínico

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

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT01002079	Completed	Alzheimer Disease	Bristol-Myers Squibb\|PRA Health Sciences	August 2010	Phase 1
NCT01057030	Completed	Alzheimer Disease	Bristol-Myers Squibb	March 2010	Phase 1
NCT01042314	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT01039194	Completed	Alzheimer Disease	Bristol-Myers Squibb	January 2010	Phase 1
NCT00979316	Completed	Alzheimer Disease	Bristol-Myers Squibb	September 2009	Phase 1
NCT00890890	Terminated	Alzheimer''s Disease	Bristol-Myers Squibb	May 2009	Phase 2

Soporte técnico

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Avagacestat (BMS-708163) Secretase inhibidor

Estructura química

Peso molecular: 520.88