Home MAPK MEK inhibitor AZD8330

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AZD8330 MEK inhibitor

Cat.No.S2134

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

Chemical Structure

Molecular Weight: 461.23

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Chemical Information, Storage & Stability

Molecular Weight 461.23 Formula

C16H17FIN3O4

 Storage (From the date of receipt)
CAS No. 869357-68-6 Download SDF Storage of Stock Solutions

Synonyms ARRY704 Smiles CC1=CC(=C(N(C1=O)C)NC2=C(C=C(C=C2)I)F)C(=O)NOCCO

Solubility

In vitro
Batch:

DMSO : 92 mg/mL (199.46 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 92 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
ERK phosphorylation [1]
0.4 nM
MEK1/2 [1]
7 nM
In vitro
AZD8330 potently and strongly inhibits MEK 1/2. This compound has no inhibitory activity against over 200 other kinases including at concentrations up to 10 μM. It 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.
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, this compound inhibits tumor growth in a dose-dependent fashion, at 0.3 mg/kg and 1.0 mg/kg once daily. [1]
References

Applications

Methods Biomarkers Images PMID
Western blot pERK / ERK / Myc / RPIA S2134-WB1 30470748
Growth inhibition assay IC50 S2134-viability1 30470748

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00454090 Completed
Cancer
AstraZeneca
 March 2007 Phase 1

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