| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
AZD8330 (AZD-8330; ARRY-704; ARRY-424704) is an orally bioactive and non-ATP competitive (Allosteric) MEK 1/2 inhibitor with potential anticancer activity. It has an IC50 of 7 nM for MEK1/2 inhibition.
| Targets |
MEK1 (IC50 = 7 nM); MEK2 (IC50 = 7 nM)
|
|---|---|
| ln Vitro |
AZD8330 is a selective allosteric MEK1/ MEK2 inhibitor. Loss of ERK phosphorylation indicates effective MEK inhibition when the human osteosarcoma cell lines MOS, U2OS, and 143B are exposed to 0.5 μM of trametinib, AZD8330, or TAK-733 for 6 hours. Six osteosarcoma cell lines—MOS, U2OS, KPD, ZK58, 143b, and Saos-2—are used to test the activity of these three inhibitors at different concentrations. All three inhibitors have a significant negative impact on 143b and reduce the viability of MOS and U2OS. However, none of the three inhibitors affect the viability of KPD, ZK58, or Saos-2[2].
|
| ln Vivo |
At tolerated doses (1.0 mg/kg once daily [OD]), AZD8330 exhibits a dose-dependent tumour growth inhibition of 90% in tumor xenograft models[1].
|
| Enzyme Assay |
MEK1 (S218D, S222D ΔR4F) is expressed in baculovirus-infected Hi5 insect cells and purified using immobilized metal affinity chromatography, ion exchange, and gel filtration. MEK1 is also NH2-terminally hexahistidine-tagged and constitutively active. When [γ- 33P]phosphate from [γ- 33P]ATP is incorporated onto ERK2, it is possible to measure the activity of MEK1 in the body. An incubation solution (100 μL) consisting 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) is used in the assay. The addition of 10 μM ATP (with 0.5 μC k[γ-33P]ATP/well) starts the reactions, which are then allowed to proceed for 45 min at room temperature. For the purpose of stopping the reaction and precipitating the proteins, an equal volume of 25% trichloracetic acid is added. The excess labeled ATP is removed with 0.5% phosphoric acid, the precipitated proteins are trapped on glass fiber B filter plates, and radioactivity is measured using a liquid scintillation counter. By changing the concentration of ATP in the reaction mixture, ATP dependence can be identified. The data have been fitted globally.
|
| Cell Assay |
Malme-3M melanoma cells are plated in 96-wells and subjected to AZD8330 treatments in a range of concentrations for an hour at 37 °C. Anti-phospho-ERK and anti-ERK 1/2 antibodies are incubated with the cells after they have been fixed and permeabilized. Secondary antibodies that have been fluorescently labeled are added after washing the plates. Utilizing a LICOR fluorescence imager, plates are examined. The total ERK signal is used to normalize the pERK signal.
|
| Animal Protocol |
Female nude rats (NIH rnu/rnu) with Calu-6 cells, nude rats with SW620 cells
0.3 mg/kg, 1 mg/kg Oral administration |
| References | |
| Additional Infomation |
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxo-3-pyridinecarboxamide is a pyridinecarboxamide. It is functionally related to a nicotinamide.
AZD-8330 is a potent, selective, orally active MEK inhibitor that blocks signal transduction pathways implicated in cancer cell proliferation and survival. AZD-8330 has shown tumor suppressive activity in multiple preclinical models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. MEK Inhibitor AZD8330 is an orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor AZD8330 specifically inhibits mitogen-activated protein kinase kinase 1 (MEK or MAP/ERK kinase1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers. Drug Indication Investigated for use/treatment in cancer/tumors (unspecified). Mechanism of Action AZD8330 specifically inhibits mitogen-activated protein kinase kinase 1 (MEK or MAP/ERK kinase1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers. |
| Molecular Formula |
C16H17FIN3O4
|
|
|---|---|---|
| Molecular Weight |
461.23
|
|
| Exact Mass |
461.024
|
|
| Elemental Analysis |
C, 41.67; H, 3.72; F, 4.12; I, 27.51; N, 9.11; O, 13.88.
|
|
| CAS # |
869357-68-6
|
|
| Related CAS # |
|
|
| PubChem CID |
16666708
|
|
| Appearance |
Off-white to pink solid powder
|
|
| Density |
1.7±0.1 g/cm3
|
|
| Index of Refraction |
1.659
|
|
| LogP |
2.05
|
|
| Hydrogen Bond Donor Count |
3
|
|
| Hydrogen Bond Acceptor Count |
6
|
|
| Rotatable Bond Count |
6
|
|
| Heavy Atom Count |
25
|
|
| Complexity |
596
|
|
| Defined Atom Stereocenter Count |
0
|
|
| SMILES |
O=C(C1=C(NC2C(F)=CC(I)=CC=2)N(C)C(=O)C(C)=C1)NOCCO
|
|
| InChi Key |
RWEVIPRMPFNTLO-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C16H17FIN3O4/c1-9-7-11(15(23)20-25-6-5-22)14(21(2)16(9)24)19-13-4-3-10(18)8-12(13)17/h3-4,7-8,19,22H,5-6H2,1-2H3,(H,20,23)
|
|
| Chemical Name |
2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1,5-dimethyl-6-oxopyridine-3-carboxamide
|
|
| Synonyms |
ARRY704; AZD 8330; AZD8330; ARRY424704; ARRY-704; ARRY 424704; ARRY 704; ARRY-424704; AZD-8330
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3.25 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 3.25 mg/mL (7.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% hydroxyethyl cellulose+0.1% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1681 mL | 10.8406 mL | 21.6812 mL | |
| 5 mM | 0.4336 mL | 2.1681 mL | 4.3362 mL | |
| 10 mM | 0.2168 mL | 1.0841 mL | 2.1681 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00454090 | Completed | Drug: AZD8330 | Cancer | AstraZeneca | March 2007 | Phase 1 |
Selection of hits in two human osteosarcoma cell lines.Genes Cancer.2015 Nov;6(11-12):503-12. |
Validation of three MEK inhibitors in 6 osteosarcoma cell lines.Genes Cancer.2015 Nov;6(11-12):503-12. |
Validation of sensitivity to MEK inhibitors in a 3D culture system.Genes Cancer.2015 Nov;6(11-12):503-12. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
