Name: Avapritinib (BLU-285)
Brand: Selleck Chemicals
SKU: S8553
Rating: 5 (14 reviews)

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Contrôle qualité

Lot : Pureté : 99.99%

99.99

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

Culture cellulaire, traitement et concentration de travail

Lignées cellulaires	Type dessai	Temps dincubation	Description de lactivité	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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Informations chimiques, stockage et stabilité

Poids moléculaire	498.56	Formule	C₂₆H₂₇FN₁₀	Stockage (À partir de la date de réception)	3 ans-20°Cpoudre
N° CAS	1703793-34-3	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	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

Solubilité

In vitro
Lot:

DMSO : 100 mg/mL (200.57 mM)
(Le DMSO contaminé par lhumidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Ethanol : 1.5 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.
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 Validé par les laboratoires Selleck. Si vous avez besoin dajustements à cette formulation, contactez notre équipe de vente pour des tests personnalisés.	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.

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	PDGFRα (D842V) 0.5 nM c-Kit (D816V) 0.5 nM
In vitro	Avapritinib (BLU-285) est un inhibiteur oral sélectif qui cible les mutants de l'exon 17 de KIT et de la boucle d'activation PDGFRα D842. Des essais cellulaires mesurant l'inhibition de l'autophosphorylation du mutant KIT confirment son activité contre les mutants KIT D816 D816V (cellules HMC1.2, IC50 = 3 nM) et D816Y (cellules P815, IC50 = 22 nM) ainsi que d'autres mutants de l'exon 17 de KIT tels que N822K (cellules Kasumi, IC50 = 40 nM) trouvés dans les GIST réfractaires au traitement.
In vivo	In vivo, Avapritinib (BLU-285) est un agent bien toléré, biodisponible par voie orale, qui entraîne une inhibition de la croissance tumorale dose-dépendante dans un modèle de xénogreffe piloté par D816Y. Une relation PK-PD-efficacité a été établie avec ce composé, démontrant que la régression tumorale résulte d'une suppression de la cible >90 % et est observée avec une dose de 30 mg/kg une fois par jour. Grâce à son activité puissante contre les mutants PDGFRα D842V et KIT Exon 17, il cible des moteurs génomiques de la maladie précédemment non traités et offre des promesses pour le traitement des GIST (tumeur stromale gastro-intestinale) ou SM (mastocytose systémique) pilotées par PDGFRα D842V, où plus de 90 % des patients portent la mutation KIT D816V. Outre l'activité en monothérapie, le BLU-285 hautement sélectif offre une opportunité de combinaison avec d'autres agents dans les GIST pour couvrir l'ensemble des mutants primaires et de résistance de KIT.
Références	[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

Applications

Méthodes	Biomarqueurs	Images	PMID
Western blot	PDGFRA / c-KIT / Wee1 / Cdc2 / PARP / γH2AX / CyclinD1 / β-actin		33320833

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
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

Support technique

Instructions de manipulation

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

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Avapritinib (BLU-285) inhibiteur de PDGFRα

Structure chimique

Poids moléculaire: 498.56