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

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.91%

99.91

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

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	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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Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Moleculair gewicht	453.54	Formule	C₂₇H₂₇N₅O₂	Opslag (Vanaf de ontvangstdatum)	3 jaar-20°Cpoeder
CAS-nr.	405554-55-4	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	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

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 5 mg/mL (11.02 mM)
(Met vocht verontreinigde DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Moleculair gewicht
=	×	×

Verdunningscalculator Moleculair gewicht calculator

In vivo Batch:
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 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	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.

In vivo Formuleringscalculator (Heldere oplossing)

Stap 1: Voer de onderstaande informatie in (Aanbevolen: Een extra dier voor het geval van verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in het gedeelte Oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-mastervloeistof: mg geneesmiddel vooraf opgelost in μL DMSO ( Concentratie mastervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de partij geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toeμL PEG300, mengen en helder maken, voeg vervolgens toeμL Tween 80, mengen en helder maken, voeg vervolgens toe μL ddH₂O, mengen en helder maken.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO mastervloeistof, voeg vervolgens toe μL Maïsolie, mengen en helder maken.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysische methoden zoals vortexen, echografie of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Kenmerken	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.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/17145850/ [2] https://pubmed.ncbi.nlm.nih.gov/16260133/ [3] https://pubmed.ncbi.nlm.nih.gov/18790768/

Toepassingen (Applications)

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	p-MEK / MEK / p-ERK / ERK		25879420

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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 B-Raf-remmer

Moleculair gewicht: 453.54

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

SB590885 B-Raf-remmer

Moleculair gewicht: 453.54

Kwaliteitscontrole (Quality Control)

Celkweek, behandeling & werkconcentratie (Cell Culture, Treatment & Working Concentration)

Chemische informatie, Opslag en Stabiliteit (Chemical Information, Storage & Stability)

Oplosbaarheid (Solubility)

Molariteitscalculator

In vivo Formuleringscalculator (Heldere oplossing)

Werkingsmechanisme (Mechanism of Action)

Toepassingen (Applications)

Celkweek, behandeling & werkconcentratie
(Cell Culture, Treatment & Working Concentration)