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50mg |
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250mg |
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500mg |
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Purity: ≥98%
Selumetinib (also known as AZD6244; ARRY-142886; Koselugo) is a novel, potent, highly selective and orally bioavailable small molecule MEK1 inhibitor with anticancer activity. It is an approved drug for the treatment of children with neurofibromatosis type I, a genetic nervous system disorder that causes tumors to develop on nerves. In cell-free assays, selumetinib inhibits MEK1 with an IC50 of 14 nM and ERK1/2 phosphorylation with an IC50 of 10 nM, but it has no inhibitory effect on p38, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. It has strong in vivo antitumor efficacy and excellent in vitro anti-proliferative activity.
Targets |
MEK2; MEK1 (IC50 = 14 nM); MEK (IC50 = 12 nM)
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ln Vitro |
Selumetinib is not ATP-competitive and inhibits ERK1/2 phosphorylation at IC50 levels under 40 nM. Through the inhibition of ERK1/2 and p90RSK phosphorylation, as well as the elevation of caspase-3 and caspase-7 cleavage and cleaved poly(ADP)ribose polymerase, AZD6244 also slows the growth of primary HCC cells. The p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways are not significantly impacted by AZD6244. [1] Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines are both responsive to AZD6244.[2]
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ln Vivo |
Selumetinib 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 an anti-MEK1 antibody. When recombinant ERK1 is activated by immuno-isolated MEK1 in a coupled assay with MBP as the end point, MEK kinase activity is calculated. 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 |
At a density of2.0 × 104, cells are seeded. The cells undergo two culture media rinses after 48 hours of incubation. AZD6244 is used to treat cells for 24 or 48 hours at various concentrations. The MTT assay uses 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide to measure the viability of cells. With the help of a bromodeoxyuridine kit, cell proliferation is measured.
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Animal Protocol |
HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation
50 or 100mg/kg Administered via p.o. |
References |
[1]. Mol Cancer Ther . 2007 Jan;6(1):138-46. [2]. Mol Cancer Ther . 2010 Jul;9(7):1985-94. [3]. Clin Cancer Res . 2007 Mar 1;13(5):1576-83. [4]. Mol Cancer Ther . 2007 Sep;6(9):2468-76. [5]. Mol Cancer Ther . 2007 Aug;6(8):2209-19. [6]. Clin Cancer Res . 2012 Feb 15;18(4):1051-62. [7]. Int J Oncol . 2012 Aug;41(2):712-20. [8]. J Clin Endocrinol Metab . 2008 Jun;93(6):2194-201. [9]. Proc Natl Acad Sci U S A . 2009 Dec 1;106(48):20411-6. [10]. Cancer Res . 2008 Aug 1;68(15):6145-53. [11]. J Hepatol . 2010 Jan;52(1):79-87. |
Molecular Formula |
C17H15BRCLFN4O3
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Molecular Weight |
457.68
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Exact Mass |
456.00
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Elemental Analysis |
C, 44.61; H, 3.30; Br, 17.46; Cl, 7.75; F, 4.15; N, 12.24; O, 10.49
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CAS # |
606143-52-6
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Related CAS # |
Selumetinib sulfate;943332-08-9
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Appearance |
white solid powder
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SMILES |
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
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InChi Key |
CYOHGALHFOKKQC-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C17H15BrClFN4O3/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/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
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Chemical Name |
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
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Synonyms |
selumetinib; ARRY-142886; AZD6244; ARRY142886; ARRY 142886; AZD-6244; AZD 6244; ARRY886; ARRY-886; ARRY 886
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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 |
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: ≥ 1 mg/mL (2.18 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 10.0 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: ≥ 1 mg/mL (2.18 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 10.0 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: ≥ 1 mg/mL (2.18 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 | 2.1849 mL | 10.9247 mL | 21.8493 mL | |
5 mM | 0.4370 mL | 2.1849 mL | 4.3699 mL | |
10 mM | 0.2185 mL | 1.0925 mL | 2.1849 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 |
NCT03326310 | Recruiting | Drug: Azacitidine Drug: Selumetinib |
Chronic Myeloid Leukemia Myelofibroses |
University of Chicago | September 4, 2018 | Phase 1 |
NCT04924608 | Active Recruiting |
Drug: Selumetinib Other: Placebo |
Neurofibromatosis 1 Plexiform Neurofibroma (PN) |
AstraZeneca | November 19, 2021 | Phase 3 |
NCT04590235 | Active Recruiting |
Drug: Selumetinib | Neurofibromatosis 1 Neurofibroma Plexiform |
AstraZeneca | December 16, 2020 | Phase 1 |
NCT05101148 | Active Recruiting |
Drug: Selumetinib | Neurofibromatosis Type 1 | AstraZeneca | July 21, 2021 | Phase 1 |
NCT03095248 | Recruiting | Drug: Selumetinib | Glioma Meningioma |
Children's Hospital Medical Center, Cincinnati |
May 8, 2017 | Phase 2 |
Structure of ARRY-142886 and its ability to inhibit enzymatic MEK1 activity.Clin Cancer Res.2007 Mar 1;13(5):1576-83. td> |
Inhibition of tumor growth and decreased tumor phospho-ERK1/2 levels in a mouse HT-29 xenograft model. Inhibition of basal and induced ERK1/2 phosphorylation in human cancer cell lines and PBMCs.Clin Cancer Res.2007 Mar 1;13(5):1576-83. td> |
Tumor growth inhibition in the mouse BxPC3 xenograft model.Clin Cancer Res.2007 Mar 1;13(5):1576-83. td> |