SB590885

Description

Biological Activity

Protocol(Only for Reference)

Chemical Information

Cell Assay: ^[1]

Animal Study: ^[1]

References

貨號 Cat. No.: S2220
規格 Size: 5~200mg
品牌 Brand: Selleckchem

SB590885

Catalog No.S2220

SB590885 is a potent B-Raf inhibitor with K_i of 0.16 nM, 11-fold greater selectivity for B-Raf over c-Raf, no inhibition to other human kinases.

Size

Price

Stock

Quantity

10mM/1mLIn DMSO	USD 277	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 214	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 844	In stock	0 1 2 3 4 5 6 7 8 9 10
200mg	USD 2482	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Cell lines	Colo205, HT29, A375P, SKMEL28, and MALME-3M
Concentrations	Dissolved in DMSO, final concentrations ~10 μM
Incubation Time	72 hours
Method	Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.

Animal Models	Female nude mice injected s.c. with of A375P cells
Dosages	50 mg/kg/day
Administration	Injection i.p.
Solubility	2% Cremophor EL, 2% N,N-dimethylacetamide, pH 5.0, 30 mg/mL

Description

SB590885 is a potent B-Raf inhibitor with K_i of 0.16 nM, 11-fold greater selectivity for B-Raf over c-Raf, no inhibition to other human kinases.

0.16 nM (K_i) ^[1]

In vitro

SB590885 displays significant selectivity for B-Raf over c-Raf with K_i of 0.16 nM over 1.72 nM. SB-590885 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). SB590885 displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, SB590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-RafV600E, SB590885 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. SB590885 decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner. ^[1] SB590885 displays high affinity for B-Raf with Kd of 0.3 nM. ^[2] Most of the melanoma cell lines that harbor the BRAF V600E mutation and lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to SB590885 with IC50 of <1 μM. Increased levels of cyclin D1 resulting from genomic amplification mediate SB590885 resistance in B-Raf V600E-mutated melanomas. ^[3]

Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth. ^[1]

Displays significant selectivity for B-Raf over c-Raf.

Download SB590885 SDF

Molecular Weight (MW)	453.54
Formula	C₂₇H₂₇N₅O₂
CAS No.	405554-55-4

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	GSK2118436

Solubility (25°C) *	In vitro	DMSO	5 mg/mL (11 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	2% Cremophor EL, 2% N,N-dimethylacetamide, pH 5.0,	30 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.