Selumetinib (AZD6244)

Catalog No.S1008 Batch:S100837

Print

Technical Data

Formula

C17H15BrClFN4O3
Molecular Weight 457.68 CAS No. 606143-52-6
Solubility (25°C)* In vitro DMSO 92 mg/mL (201.01 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Selumetinib (AZD6244, ARRY-142886) is a potent, highly selective MEK inhibitor with IC50 of 14 nM for MEK1 and Kd value of 530 nM for MEK2. It also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Selumetinib suppresses cell proliferation, migration and trigger apoptosis. Phase 3.
Targets
MEK1 [1]
(Cell-free assay)		 MEK1 [13]
(Cell-free assay)		 MEK2 [13]
(Cell-free assay)
14 nM 99 nM(Kd) 530 nM(Kd)
In vitro AZD6244 is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. AZD6244 also inhibits the growth of primary HCC cells through inhibition of ERK1/2 and p90RSK phosphorylation, accompanied with elevation of the cleavage of caspase-3 and caspase-7, and cleaved poly(ADP)ribose polymerase. AZD6244 has little effects on the p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. [1] AZD6244 is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines. [2]
In 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. [1] AZD6244 could inhibit the tumor growth in HT-29 xenograft, which is a colorectal tumor model carrying a B-Raf mutation, at a dose of 100 mg/kg and the tumor growth inhibition of AZD6244 is better than it of Gemcitabine. [3] Otherwise AZD6244 could inhibit HCC xenografts tumor growth, which associated with increased apoptosis and down-regulation of cell cycle regulators, including cyclin D1, Cdc-2, CDK2 and 4, cyclin B1, and c-Myc. [4]
Features First MEK inhibitor being tested in Phase II clinical trials.

Protocol (from reference)

Kinase Assay:

[1]
  • Assay of MEK Kinase Activity

    Anti-MEK1 antibody is used to immunoprecipitate MEK1 molecules. MEK kinase activity is measured as the ability of immuno-isolated MEK1 to activate recombinant ERK1 in a coupled assay using MBP as the end point of the assay. Phosphorylated MBP is resolved on a 14% SDS-PAGE gel and vacuum-dried before exposure to X-ray film.
Cell Assay:

[1]
  • Cell lines

    Primary HCC cell lines including 2-1318, 4-1318 and 26-1004 cells

  • Concentrations

    ~ 10 μM

  • Incubation Time

    24 or 48 hours

  • Method

    Cells are seeded at a density of 2.0 × 104. After 48 hours incubation, the cells are rinsed twice with culture media. Cells are treated with various concentrations of AZD6244 for 24 or 48 hours. Cell viability is determined by the 3-(4,5-dimethylthiazol-2y1)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation is assayed using a bromodeoxyuridine kit.
Animal Study:

[1]
  • Animal Models

    HCC xenografts in mice homozygous for the SCID (severe combined immunodeficiency) mutation

  • Dosages

    50 or 100mg/kg

  • Administration

    Administered via p.o.

Customer Product Validation

Data from [Oncogene, 2012, 31, 3277–3286]

Data from [Nature, 2010, 468, 968-972]

Data from [Nature, 2010, 468, 973-977]

Data from [Clin Cancer Res, 2010, 16, 6029-6039]

Selleck's Selumetinib (AZD6244) has been cited by 745 publications

Combined KRAS-MAPK pathway inhibitors and HER2-directed drug conjugate is efficacious in pancreatic cancer [ Nat Commun, 2024, 15(1):2503] PubMed: 38509064
A senescence restriction point acting on chromatin integrates oncogenic signals [ Cell Rep, 2024, 43(4):114044] PubMed: 38568812
MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet [ iScience, 2024, 27(1):108696] PubMed: 38205246
Conditionally replicative adenovirus as a therapy for malignant peripheral nerve sheath tumors [ Mol Ther Oncolytics, 2024, 32(2):200783] PubMed: 38595983
Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Plexiform Neurofibroma Cells at Doses That Do Not Affect Patient-Matched Schwann Cells [ Pharmaceutics, 2024, 16(3)371] PubMed: 38543265
The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells [ World J Oncol, 2024, 15(2):192-208] PubMed: 38545471
Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway [ Nat Cancer, 2023, 4(3):419-435] PubMed: 36973439
Apoptosis-induced nuclear expulsion in tumor cells drives S100a4-mediated metastatic outgrowth through the RAGE pathway [ Nat Cancer, 2023, 4(3):419-435] PubMed: 36973439
Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration [ Protein Cell, 2023, 14(5):350-368] PubMed: 37155312
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] PubMed: 36736316

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.