Name: Avapritinib (BLU-285)
Brand: Selleck Chemicals
SKU: S8553
Rating: 5 (15 reviews)

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Control de calidad (Quality Control)

Lote: Pureza: 99.99%

99.99

Dianas relacionadas	EGFR VEGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2 c-Kit
Otros PDGFR Inhibidores	CP-673451 Orantinib (SU6668) Tyrphostin AG 1296 Trapidil PP121 AZD2932 Sennoside B Tyrphostin AG1433 Seralutinib (GB002) N-(p-Coumaroyl) Serotonin

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Líneas celulares	Tipo de ensayo	Tiempo de incubación	Descripción de la actividad	PMID
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.008 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.01 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.017 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.019 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.022 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.028 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.029 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.042 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.069 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.078 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.117 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.167 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.292 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.427 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.751 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.86 μM.	30204441
BA/F3 cells	Cytotoxicity assay	72 h	Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 4.075 μM.	30204441
BA/F3 cells	Growth inhibiton assay	72 h	Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 4.952 μM.	30204441
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Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Peso molecular	498.56	Fórmula	C₂₆H₂₇FN₁₀	Almacenamiento (Desde la fecha de recepción)	3 años-20°Cpolvo
Nº CAS	1703793-34-3	Descargar SDF		Almacenamiento de soluciones madre	1 año-80°Cen disolvente 1 mes-20°Cen disolvente
Sinónimos	BLU-285			Smiles	CC(C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N

Solubilidad (Solubility)

In vitro
Lote:

DMSO : 100 mg/mL (200.57 mM)
(El DMSO contaminado con humedad puede reducir la solubilidad. Usar DMSO fresco y anhidro.)

Ethanol : 1.5 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.
Clear solution	2%DMSO 1 40%PEG300 2 2%Tween80 3 56%ddH2O Validado por los laboratorios Selleck. Si necesita ajustes en esta formulación, contacte con nuestro equipo de ventas para pruebas personalizadas.	4.000mg/ml (8.02mM)	Taking the 1 mL working solution as an example, add 20 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 560 μL of ddH2O to adjust the volume to 1 mL. 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.

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 (Mechanism of Action)

Targets/IC₅₀/Ki	PDGFRα (D842V) 0.5 nM c-Kit (D816V) 0.5 nM
In vitro	Avapritinib (BLU-285) es un inhibidor oral selectivo que se dirige a los mutantes del bucle de activación de KIT Exon 17 y PDGFRα D842. Los ensayos celulares que miden la inhibición de la autofosforilación de los mutantes KIT confirman su actividad contra los mutantes KIT D816 D816V (células HMC1.2, IC50 = 3 nM) y D816Y (células P815, IC50 = 22 nM), así como contra otros mutantes de KIT Exon 17 como N822K (células Kasumi, IC50 = 40 nM) encontrados en GIST refractarios al tratamiento.
In vivo	In vivo, Avapritinib (BLU-285) es un agente bien tolerado y biodisponible por vía oral que logra una inhibición del crecimiento tumoral dependiente de la dosis en un modelo de xenoinjerto impulsado por D816Y. Se ha establecido una relación PK-PD-eficacia con este compuesto, demostrando que la regresión tumoral resulta de una supresión del objetivo superior al 90% y se observa con una dosis de 30 mg/kg una vez al día. Con una potente actividad contra los mutantes PDGFRα D842V y KIT Exon 17, se dirige a impulsores genómicos de la enfermedad previamente no abordados y ofrece esperanzas para el tratamiento de GIST (tumor del estroma gastrointestinal) o SM (mastocitosis sistémica) impulsados por PDGFRα D842V, donde más del 90% de los pacientes portan la mutación KIT D816V. Además de la actividad como agente ónico, el altamente selectivo BLU-285 ofrece una oportunidad de combinación con otros agentes en GIST para cubrir la totalidad de los mutantes primarios y de resistencia de KIT.
Referencias	[1] http://cancerres.aacrjournals.org/content/75/15_Supplement/791 [2] https://aacrjournals.org/cancerres/article/75/15_Supplement/791/605110/Abstract-791-BLU-285-the-first-selective-inhibitor

Aplicaciones (Applications)

Métodos	Biomarcadores	Imágenes	PMID
Western blot	PDGFRA / c-KIT / Wee1 / Cdc2 / PARP / γH2AX / CyclinD1 / β-actin		33320833

Información del ensayo clínico (Clinical Trial Information)

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

Número NCT	Reclutamiento	Condiciones	Patrocinador/Colaboradores	Fecha de inicio	Fases
NCT04908176	Completed	Gastrointestinal Stromal Tumors\|GIST\|Non-resectable Advanced Solid Tumors\|Recurrent or Unresectable Central Nervous System (CNS) Tumors	Blueprint Medicines Corporation	August 24 2022	Phase 1
NCT04695431	Completed	Advanced Systemic Mastocytosis\|Aggressive Systemic Mastocytosis\|Systemic Mastocytosis With an Associated Hematological Neoplasm\|Mast Cell Leukemia	Blueprint Medicines Corporation\|Analysis Group Inc.	December 2 2020	--
NCT03731260	Active not recruiting	Indolent Systemic Mastocytosis	Blueprint Medicines Corporation	April 16 2019	Phase 2
NCT03580655	Active not recruiting	Advanced Systemic Mastocytosis\|Aggressive Systemic Mastocytosis\|Systemic Mastocytosis With an Associated Hematologic Neoplasm\|Mast Cell Leukemia	Blueprint Medicines Corporation	November 21 2018	Phase 2
NCT03465722	Completed	GIST	Blueprint Medicines Corporation	March 26 2018	Phase 3

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
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):

Avapritinib (BLU-285) PDGFRα inhibitor

Estructura química

Peso molecular: 498.56

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Avapritinib (BLU-285) PDGFRα inhibitor

Estructura química

Peso molecular: 498.56

Control de calidad (Quality Control)

Cultivo celular, tratamiento y concentración de trabajo (Cell Culture, Treatment & Working Concentration)

Información química, almacenamiento y estabilidad (Chemical Information, Storage & Stability)

Solubilidad (Solubility)

Calculadora de Molaridad

Calculadora de formulación in vivo (Solución clara)

Mecanismo de acción (Mechanism of Action)

Aplicaciones (Applications)

Información del ensayo clínico (Clinical Trial Information)

Cultivo celular, tratamiento y concentración de trabajo
(Cell Culture, Treatment & Working Concentration)