Home MAPK MEK inhibitor AZD8330 For research use only.

AZD8330

Synonyms: ARRY704

AZD8330 (ARRY704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1.

AZD8330 Chemical Structure

AZD8330 Chemical Structure

CAS No. 869357-68-6

Purity & Quality Control

AZD8330 Related Products

Signaling Pathway

MEK Signaling Pathways

MEK Signaling Pathway

Biological Activity

Description AZD8330 (ARRY704) is a novel, selective, non-ATP competitive MEK 1/2 inhibitor with IC50 of 7 nM. Phase 1.
Targets
ERK phosphorylation [1] MEK1/2 [1]
0.4 nM 7 nM
In vitro
In vitro AZD8330 potently and strongly inhibits MEK 1/2. AZD8330 has no inhibitory activity against over 200 other kinases including at concentrations up to 10 μM. AZD8330 demonstrates sub-nanomolar potency in mechanistic (pERK) and low to sub-nanomolar potency in functional (proliferation) assays in MEK 1/2 inhibitor sensitive cell lines. [1]
Kinase Assay MEK1 enzymatic assays
NH2-terminal hexahistidine tagged, constitutively active MEK1 (S218D, S222D ΔR4F) is expressed in baculovirus-infected Hi5 insect cells and purified by immobilized metal affinity chromatography, ion exchange, and gel filtration. The activity of MEK1 is assessed by measuring the incorporation of [γ- 33P]phosphate from [γ-33P]ATP onto ERK2. The assay is carried out in a 96-well polypropylene plate with an incubation mixture (100 μL) composed of 25 mM HEPES (pH 7.4), 10 mM MgCl2, 5 mM β-glycerolphosphate, 100 μM sodium orthovanadate, 5 mM DTT, 5 nM MEK1, 1 μM ERK2, and 0 to 80 nM AZD8330 (final concentration of 1% DMSO). The reactions are initiated by the addition of 10 μM ATP (with 0.5 μC k[γ-33P]ATP/well) and incubated at room temperature for 45 min. An equal volume of 25% trichloracetic acid is added to stop the reaction and precipitate the proteins. Precipitated proteins are trapped onto glass fiber B filter plates, excess labeled ATP is washed off with 0.5% phosphoric acid, and radioactivity is counted in a liquid scintillation counter. ATP dependence is determined by varying the amount of ATP in the reaction mixture. The data are globally fitted.
Cell Research Cell lines Malme-3M melanoma cells
Concentrations ~10 μM
Incubation Time 1 hour
Method

Malme-3M melanoma cells are plated in 96-wells and treated with various concentrations of AZD8330 for 1 hour at 37 °C. The cells are fixed, permeabilized, and incubated with an anti-phospho-ERK antibody and an anti-ERK 1/2 antibody. Plates are washed and fluorescently-labeled secondary antibodies are added. Plates are analyzed on a LICOR fluorescence imager. The pERK signal is normalized to the total ERK signa
Experimental Result Images Methods Biomarkers Images PMID
Western blot pERK / ERK / Myc / RPIA 30470748
Growth inhibition assay IC50 30470748
In Vivo
In vivo In a Calu-6 rat xenograft pharmacokinetic/pharmacodynamic (PK/PD) model a single, 1.25 mg/kg oral dose of AZD8330 inhibits ERK phosphorylation by > 90% for between 4 and 8 hours. Doses as low as 0.4 mg/kg once daily are sufficient for > 80% tumor growth inhibition in the Calu-6 nude rat xenograft model. In the Calu-6 model, AZD8330 inhibits tumor growth in a dose-dependent fashion, at 0.3 mg/kg and 1.0 mg/kg once daily. [1]
Animal Research Animal Models Female nude rats (NIH rnu/rnu) with Calu-6 cells, nude rats with SW620 cells
Dosages 0.3 mg/kg, 1 mg/kg
Administration Oral administration
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00454090 Completed
Cancer
AstraZeneca
 March 2007 Phase 1

Chemical Information & Solubility

Molecular Weight 461.23 Formula

C16H17FIN3O4
CAS No. 869357-68-6 SDF Download AZD8330 SDF
Smiles CC1=CC(=C(N(C1=O)C)NC2=C(C=C(C=C2)I)F)C(=O)NOCCO
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 92 mg/mL ( (199.46 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 92 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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