Name: SB590885
Brand: Selleck Chemicals
SKU: S2220
Rating: 5 (42 reviews)

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Contrôle Qualité (Quality Control)

Lot : Pureté : 99.91%

99.91

Cibles apparentées	ERK p38 MAPK JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Autre Raf Inhibiteurs	LY3009120 Exarafenib (KIN-2787) GDC-0879 Avutometinib (Ro5126766, CH5126766) PLX-4720 AZ 628 TAK-632 GW5074 RAF265 (CHIR-265) PLX7904

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Lignées cellulaires	Type d'essai	Concentration	Temps d'incubation	Description de l'activité	PMID
Sf9	Function assay			Binding affinity to human N-His6-tagged B-Raf expressed in Sf9 cells, Kd=0.00016μM	22024030
white blood cells	Antifibrotic assay	25 to 150 mg/kg	13 days	Antifibrotic activity in bleomycin-induced C57B1/6 mouse model assessed as inhibition of white blood cells in bronchoalveolar lavage at 25 to 150 mg/kg, po bid administered 2 hrs prior bleomycin induction for 13 days	22222036
insect cells	Function assay		30 mins	Inhibition of full length human 6His-tagged BRAF V600E mutant expressed in baculovirus infected insect cells co-expressing human CDC37 (1 to 378 residues) using MEK1 as substrate after 30 mins, IC50=0.00016μM	29461827
A549	Function assay		60 mins	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human A549 cells after 60 mins by Western blot analysis, EC50=0.028μM	22222036
Colo205	Function assay		60 mins	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human Colo205 cells after 60 mins by Western blot analysis, EC50=0.028μM	22222036
HT-29	Function assay		60 mins	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human HT-29 cells after 60 mins by Western blot analysis, EC50=0.028μM	22222036
MALME3M	Function assay		60 mins	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human MALME3M cells after 60 mins by Western blot analysis, EC50=0.028μM	22222036
SKMEL28	Function assay		60 mins	Inhibition of B-Raf V600E mutant-mediated Erk phosphorylation in human SKMEL28 cells after 60 mins by Western blot analysis, EC50=0.028μM	22222036
A375	Function assay			Inhibition of b-Raf in human A375 cells assessed phosphorylation of ERK, IC50=0.29μM	22808911
A375	Function assay			Inhibition of BRAF V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation by immunoblot analysis, IC50=0.29μM	29461827
A375	Antiproliferative assay			Antiproliferative activity against human A375 cells expressing B-Raf V600E mutant and wild type Ras, IC50=0.37μM	22808911
A375	Cytotoxicity assay		48 hrs	Cytotoxicity against human A375 cells harboring BRAF V600E mutant after 48 hrs by CellTiter-Glo assay, IC50=0.37μM	29461827
HFF	Function assay		60 mins	Inhibition of B-Raf-mediated Erk phosphorylation in human HFF cells after 60 mins by Western blot analysis, EC50=1.1μM	22222036
HMEC	Function assay		60 mins	Inhibition of B-Raf-mediated Erk phosphorylation in human HMEC cells after 60 mins by Western blot analysis, EC50=1.1μM	22222036
PREC	Function assay		60 mins	Inhibition of B-Raf-mediated Erk phosphorylation in human PREC cells after 60 mins by Western blot analysis, EC50=1.1μM	22222036
HCT116	Growth inhibition assay		72 hrs	Growth inhibition of human HCT116 cells expressing wild-type B-Raf and K-Ras2 G13D mutant after 72 hrs by WST-1 assay, EC50=1.1μM	22222036
SK-MEL-2	Growth inhibition assay		72 hrs	Growth inhibition of human SK-MEL-2 cells expressing wild-type B-Raf and N-Ras2 Q61R mutant after 72 hrs by WST-1 assay, EC50=1.1μM	22222036
HCT116	Antiproliferative assay			Antiproliferative activity against human HCT116 cells expressing wild type b-Raf and KRAS mutant, IC50=4.6μM	22808911
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Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Poids moléculaire	453.54	Formule	C₂₇H₂₇N₅O₂	Stockage (À compter de la date de réception)	3 ans-20°Cpoudre
N° CAS	405554-55-4	Télécharger le SDF		Stockage des solutions mères	1 an-80°Cen solvant 1 mois-20°Cen solvant
Synonymes	N/A			Smiles	CN(C)CCOC1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC5=C(C=C4)C(=NO)CC5

Solubilité (Solubility)

In vitro
Lot:

DMSO : 5 mg/mL (11.02 mM)
(Le DMSO contaminé par l'humidité peut réduire la solubilité. Utiliser du DMSO frais et anhydre.)

Water : Insoluble

Ethanol : 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% Cremophor EL 1 2% N 2 N-dimethylacetamide 3 pH 5.0 Validé par les laboratoires Selleck. Si vous avez besoin d'ajustements à cette formulation, contactez notre équipe commerciale pour des tests personnalisés.	30.000mg/ml (66.15mM)
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 : Saisir les informations ci-dessous (Recommandé : Un animal supplémentaire pour tenir compte des pertes pendant l'expérience)

Dosage : mg/kg Poids moyen des animaux : g Volume de dosage par animal :μL Nombre d'animaux :

Étape 2 : Saisir la formulation in vivo (Ceci est seulement le calculateur, pas la formulation. Veuillez nous contacter d'abord s'il n'y 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 d'abord 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, puis ajouterμL PEG300, mélanger et clarifier, puis ajouterμL Tween 80, mélanger et clarifier, puis ajouter μL ddH₂O, mélanger et clarifier.

Méthode de préparation de la formulation in vivo : Prendre μL DMSO liquide maître, puis ajouter μL Huile de maïs, mélanger et clarifier.

Note : 1. Veuillez vous assurer que le liquide est clair avant d'ajouter le solvant suivant.
2. Assurez-vous d'ajouter le(s) solvant(s) dans l'ordre. Vous devez vous assurer que la solution obtenue, lors de l'ajout précédent, est une solution claire avant de procéder à l'ajout du solvant suivant. Des méthodes physiques telles que le vortex, les ultrasons ou le bain-marie chaud peuvent être utilisées pour faciliter la dissolution.

Mécanisme d'action (Mechanism of Action)

Caractéristiques	Displays significant selectivity for B-Raf over c-Raf.
Targets/IC₅₀/Ki	B-Raf (Cell-free assay) 0.16 nM(Ki)
In vitro	SB590885 displays significant selectivity for B-Raf over c-Raf with K_i of 0.16 nM over 1.72 nM. This compound is a more potent inhibitor than the previously described Raf/VEGFR kinase inhibitor BAY 439006 (K_i = 38 nM for mutant B-Raf, 6 nM for c-Raf). It displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, this chemical stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-RafV600E, this compound treatment potently inhibits ERK phosphorylation with EC50 of 28 nM, 58 nM, 290 nM, 58 nM, and 190 nM, respectively, and consistently, inhibits the proliferation with EC50 of 0.1 μM, 0.87 μM, 0.37 μM, 0.12 μM, and 0.15 μM, respectively. It decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner. This chemical displays high affinity for B-Raf with Kd of 0.3 nM. Most of the melanoma cell lines that harbor the BRAF V600E mutation and lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to this compound with IC50 of <1 μM. Increased levels of cyclin D1 resulting from genomic amplification mediate this compound resistance in B-Raf V600E-mutated melanomas.
In vivo	Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth.
Références	[1] https://pubmed.ncbi.nlm.nih.gov/17145850/ [2] https://pubmed.ncbi.nlm.nih.gov/16260133/ [3] https://pubmed.ncbi.nlm.nih.gov/18790768/

Applications (Applications)

Méthodes	Biomarqueurs	Images	PMID
Western blot	p-MEK / MEK / p-ERK / ERK		25879420

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):

SB590885 Inhibiteur de B-Raf

Poids moléculaire: 453.54

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

SB590885 Inhibiteur de B-Raf

Poids moléculaire: 453.54

Contrôle Qualité (Quality Control)

Culture cellulaire, traitement et concentration de travail (Cell Culture, Treatment & Working Concentration)

Informations chimiques, stockage et stabilité (Chemical Information, Storage & Stability)

Solubilité (Solubility)

Calculateur de molarité

Calculateur de formulation in vivo (Solution claire)

Mécanisme d'action (Mechanism of Action)

Applications (Applications)

Culture cellulaire, traitement et concentration de travail
(Cell Culture, Treatment & Working Concentration)