Selumetinib (AZD-6244; ARRY142886)

Alias: selumetinib; ARRY-142886; AZD6244; ARRY142886; ARRY 142886; AZD-6244; AZD 6244; ARRY886; ARRY-886; ARRY 886
Cat No.:V0444 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.
Selumetinib (AZD-6244; ARRY142886) Chemical Structure CAS No.: 606143-52-6
Product category: MEK
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
50mg
100mg
250mg
500mg
1g
2g
Other Sizes

Other Forms of Selumetinib (AZD-6244; ARRY142886):

  • Selumetinib sulfate (AZD6244 sulfate)
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
Targets
MEK2; MEK1 (IC50 = 14 nM); MEK (IC50 = 12 nM)
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]
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.
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.
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.
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.

[12]. Clin Cancer Res . 2011 May 1;17(9):2744-56.

[13]. Nat Biotechnol . 2011 Oct 30;29(11):1046-51.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H15BRCLFN4O3
Molecular Weight
457.68
Exact Mass
456.00
Elemental Analysis
C, 44.61; H, 3.30; Br, 17.46; Cl, 7.75; F, 4.15; N, 12.24; O, 10.49
CAS #
606143-52-6
Appearance
white solid powder
SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
InChi Key
CYOHGALHFOKKQC-UHFFFAOYSA-N
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)
Chemical Name
6-(4-bromo-2-chloroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
Synonyms
selumetinib; ARRY-142886; AZD6244; ARRY142886; ARRY 142886; AZD-6244; AZD 6244; ARRY886; ARRY-886; ARRY 886
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 Data
Solubility (In Vitro)
DMSO: ~91 mg/mL (~198.8 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In Vivo)
4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

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.

Clinical Trial Information
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
Biological Data
  • Selumetinib (AZD6244)

    Structure of ARRY-142886 and its ability to inhibit enzymatic MEK1 activity.2007 Mar 1;13(5):1576-83.

  • Selumetinib (AZD6244)

    Inhibition of tumor growth and decreased tumor phospho-ERK1/2 levels in a mouse HT-29 xenograft model.


    Selumetinib (AZD6244)

    Inhibition of basal and induced ERK1/2 phosphorylation in human cancer cell lines and PBMCs.2007 Mar 1;13(5):1576-83.

  • Selumetinib (AZD6244)

    Tumor growth inhibition in the mouse BxPC3 xenograft model.2007 Mar 1;13(5):1576-83.

  • Selumetinib (AZD6244)
  • Selumetinib (AZD6244)
Contact Us