Size | Price | Stock | Qty |
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100mg |
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250mg |
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500mg |
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1g |
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2g |
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Selumetinib sulfate (also known as AZD6244 sulfate; ARRY-142886 sulfate) is a novel, potent, highly selective, orally bioavailable, and non-ATP-competitive small molecule MEK1 inhibitor with IC50 of 14 nM in cell-free assays and with anticancer activity, it also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib prevents the activation of MEK1/2-dependent effector proteins and transcription factors, which may prevent the proliferation of MEK-overexpressing tumor cells by preventing the activation of MEK1/2-dependent effector proteins and transcription factors.
Targets |
MEK1 (IC50 = 14 nM); MEK1 (Kd = 99 nM); MEK2 (Kd = 530 nM)
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ln Vitro |
NVP-BHG712 dose-dependently inhibited the autophosphorylation of EphRs in Hek293 cells transfected with various EphRs. When compared to EphB2, EphA2, EphB3, and NVP-BHG712, EphB4 exhibited a stronger inhibitory preference. AZD6244 inhibits the phosphorylation of ERK1/2 at IC50 concentrations below 40 nM and is not ATP-competitive. Inhibiting ERK1/2 and p90RSK phosphorylation, as well as elevating caspase-3 and caspase-7 cleavage and cleaved poly(ADP)ribose polymerase, all contribute to AZD6244's ability to stop the growth of primary HCC cells. Phosphatidylinositol 3-kinase, MEK5/ERK5 and p38 pathways are not significantly affected by AZD6244. Ras mutations and Raf mutations both affect AZD6244's sensitivity to breast cancer cell lines and NSCLC cell lines, respectively.
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ln Vivo |
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. At a dose of 100 mg/kg, AZD6244 could slow the growth of the tumor in the HT-29 xenograft, a colorectal tumor model with a B-Raf mutation; this tumor growth inhibition is superior to that of Gemcitabine. Apoptosis and the down-regulation of cell cycle regulators like cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc are associated with increased apoptosis, which is why AZD6244 could inhibit the growth of HCC xenograft tumors in the absence of these factors.
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Enzyme Assay |
MEK1 molecules are immunoprecipitated using anti-MEK1 antibodies. Measuring MEK kinase activity involves using immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay with MBP as the end point. Before being exposed to X-ray film, phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum dried.
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Cell Assay |
Cells are seeded at a density of 2.0 × 104 (Primary HCC cell lines, including 2-1318, 4-1318, and 26-1004 cells). The cells are rinsed twice with culture media after 48 hours of incubation. AZD6244 is applied to cells at various concentrations for 24 or 48 hours. The 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay is used to determine the viability of cells. A bromodeoxyuridine kit is used to measure cell proliferation.
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Animal Protocol |
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References |
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Molecular Formula |
C₁₇H₁₇BRCLFN₄O₇S
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Molecular Weight |
555.76
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Exact Mass |
553.96739
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CAS # |
943332-08-9
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Related CAS # |
Selumetinib;606143-52-6
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Appearance |
Solid
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SMILES |
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO.OS(=O)(=O)O
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InChi Key |
GRKFGZYYYYISDX-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C17H15BrClFN4O3.H2O4S/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19;1-5(2,3)4/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26);(H2,1,2,3,4)
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Chemical Name |
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide;sulfuric acid
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.50 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: ≥ 2.5 mg/mL (4.50 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 25.0 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: ≥ 2.5 mg/mL (4.50 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: 4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.7993 mL | 8.9967 mL | 17.9934 mL | |
5 mM | 0.3599 mL | 1.7993 mL | 3.5987 mL | |
10 mM | 0.1799 mL | 0.8997 mL | 1.7993 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 |
NCT03213691 | Active Recruiting |
Drug: Selumetinib Sulfate Drug: Selumetinib |
Recurrent Neuroblastoma Refractory Neuroblastoma |
National Cancer Institute (NCI) |
July 24, 2017 | Phase 2 |
NCT02839720 | Active Recruiting |
Other: Laboratory Biomarker Analysis Drug: Selumetinib Sulfate |
Optic Nerve Glioma Cutaneous Neurofibroma |
National Cancer Institute (NCI) |
August 26, 2017 | Phase 2 |
NCT01362803 | Active Recruiting |
Drug: AZD6244 | Neurofibromatosis 1 NF1 |
National Cancer Institute (NCI) |
September 21, 2011 | Phase 1 Phase 2 |
NCT01364051 | Active Recruiting |
Drug: Cediranib Drug: Selumetinib |
Metastatic Melanoma Refractory Malignant National Cancer Institute |
(NCI) May 25, 2011 |
Phase 1 |
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NCT02407405 | Active Recruiting |
Drug: Selumetinib | Neurofibromatosis 1 (NF1) Plexiform Neurofibromas (PN) |
National Cancer Institute (NCI) |
January 7, 2016 | Phase 2 |