Selumetinib (AZD6244)

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

Preparing Stock Solutions

Customer Reviews (11)

Kinase Assay:

^[1]

Cell Assay:

^[1]

Animal Study:

^[1]

References

貨號 Cat. No.: S1008
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Selumetinib (AZD6244)

Catalog No.S1008

11 Reviews 60 Product Citations

Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 1/2.

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Quantity

10mM/1mLIn DMSO	USD 147	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 113	In stock	0 1 2 3 4 5 6 7 8 9 10
100mg	USD 163	In stock	0 1 2 3 4 5 6 7 8 9 10
200mg	USD 214	In stock	0 1 2 3 4 5 6 7 8 9 10
500mg	USD 466	In stock	0 1 2 3 4 5 6 7 8 9 10

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

Assay of MEK Kinase Activity	Anti-MEK1 antibody is used to immunoprecipitate MEK1 molecules. MEK kinase activity is measured as the ability of immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay using MBP as the end point of the assay. Phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum-dried before exposure to X-ray film.

Cell lines	Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells
Concentrations	~ 10 μM
Incubation Time	24 or 48 hours
Method	Cells are seeded at a density of 2.0 × 10⁴. After 48 hours incubation, the cells are rinsed twice with culture media. Cells are treated with various concentrations of AZD6244 for 24 or 48 hours. Cell viability is determined by the 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation is assayed using a bromodeoxyuridine kit.

Animal Models	HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
Dosages	50 or 100mg/kg
Administration	Administered via p.o.
Solubility	0.5% methylcellulose/0.2% Tween 80 30 mg/mL

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01750281	Recruiting	Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIb - IV	AstraZeneca	2012-12	Phase 2
NCT01783197	Recruiting	Non Small Cell Lung Cancer	NCIC Clinical Trials Group\|AstraZeneca	2013-01	Phase 1
NCT01859182	Terminated	Adenocarcinoma of the Gallbladder\|Adenocarcinoma With Squamous Metaplasia of the Gallbladder\|Adult Primary Cholangiocellular Carcinoma\|Advanced Adult Primary Liver Cancer etc.	National Cancer Institute (NCI)	2013-01	Phase 2
NCT01809210	Recruiting	Locally Advanced or Metastatic Non Small Cell Lung Cancer Stage IIIB -IV	AstraZeneca	2013-04	Phase 1
NCT01843062	Not yet recruiting	Differentiated Thyroid Cancer	AstraZeneca	2013-06	Phase 2

Download Selumetinib (AZD6244) SDF

Molecular Weight (MW)	457.68
Formula	C₁₇H₁₅BrClFN₄O₃
CAS No.	606143-52-6

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	ARRY-142886

Solubility (25°C) *	In vitro	DMSO	92 mg/mL (201 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	0.5% methylcellulose/0.2% Tween 80	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.

Chemical Name	6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.45768	4.5768	9.1536	13.7304

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Description

Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 1/2.

In vitro

AZD6244 is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. AZD6244 also inhibits the growth of primary HCC cells through inhibition of ERK1/2 and p90^RSKphosphorylation, accompanied with elevation of the cleavage of caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase. AZD6244 has little effects on the p38, c-Jun-NH₂-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. ^[1] AZD6244 is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines. ^[2]

AZD6244 significantly inhibits phosphorylation of ERK1/2 in 2-1318, 5-1318, 26-1004 and 4-1318 xenografts and induces apoptosis in primary 2-1318 cells by activating the caspase pathway. ^[1] AZD6244 could inhibit the tumor growth in HT-29 xenograft, which is a colorectal tumor model carrying a B-Raf mutation, at a dose of 100 mg/kg and the tumor growth inhibition of AZD6244 is better than it of Gemcitabine. ^[3] Otherwise AZD6244 could inhibit HCC xenografts tumor growth, which associated with increased apoptosis and down-regulation of cell cycle regulators, including cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc. ^[4]

First MEK inhibitor being tested in Phase II clinical trials.

Click to enlarge	Rating
	Source	Oncogene, 2012, 31, 3277–3286. Selumetinib (AZD6244) purchased from Selleck
	Method	Western Blot
	Cell Lines	HEK-293 cells
	Concentrations	1 uM
	Incubation Time
	Results	We cultured HEK-293 cellsstably overexpressing p37d or p110d with the general PI3K –inhibitor, LY294002, or the MAPK-inhibitor, AZD6244. The inhibitors strongly affected the levels ofphosphorylated AKT S473 and ERK.