AZD6244 (Selumetinib)

Catalog No.S1008 Batch:S100837

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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
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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

Selumetinib (AZD6244) is not competitive with ATP and inactivates the ERK1/2 phosphorylation with IC50 concentrations below 40 nM. It 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. This compound has little effects on the p38, c-Jun-NH2-kinase, phosphatidylinositol 3-kinase, and MEK5/ERK5 pathways. It is sensitive to Raf mutations in breast cancer cell lines and Ras mutations in NSCLC cell lines.

In vivo

Selumetinib (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. It 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 this compound is better. Otherwise it 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.

Features First MEK inhibitor being tested in Phase II clinical trials.

Protocol (from reference)

Kinase Assay:

[1]
  • Assay of MEK Kinase Activity

    Selumetinib (AZD6244) 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. They are then treated with various concentrations of Selumetinib (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.

References

  • https://pubmed.ncbi.nlm.nih.gov/17237274/
  • https://pubmed.ncbi.nlm.nih.gov/20587667/
  • https://pubmed.ncbi.nlm.nih.gov/17332304/
  • https://pubmed.ncbi.nlm.nih.gov/17876044/
  • https://pubmed.ncbi.nlm.nih.gov/17699718/
  • https://pubmed.ncbi.nlm.nih.gov/22173548/
  • https://pubmed.ncbi.nlm.nih.gov/22641227/
  • https://pubmed.ncbi.nlm.nih.gov/18381570/
  • https://pubmed.ncbi.nlm.nih.gov/19915144/
  • https://pubmed.ncbi.nlm.nih.gov/18676837/
  • https://pubmed.ncbi.nlm.nih.gov/19910069/
  • https://pubmed.ncbi.nlm.nih.gov/21385921/
  • https://pubmed.ncbi.nlm.nih.gov/22037378/

Customer Product Validation

<p>Stimulation response of p37d-expressing cells. (c) Western blot of 5 min serum stimulated HEK-293 cells stably expressing p37d, p110d or control, with the presence of inhibitors as indicated at the top.</p>

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

<p>A,ERK phosphorylation in A375 expressing indicated ORFs following treatment with DMSO or 1 μM of PLX4720, RAF265, CI-1040 or AZD6244. B,ERK phosphorylation in A375 expressing indicated ORFs following treatment with DMSO, PLX4720 (1 μM) or PLX4720 in combination with CI-1040 or AZD6244 (all 1 μM).</p>

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

<p>Survival curves for isogenic cell line pairs and melanoma cultures treated with the indicated AZD6244 concentration for 72 h (relative to DMSO treated controls; mean6s.e.m., n55). PLX4032 resistant cells were grown with PLX4032. Dashed line, 50% cell killing.</p>

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

<p>A and B, clonogenic assays in 2 melanoma cell lines (YUVON and YUSIK) treated with NVPBEZ235 (BEZ) and AZD6244 (AZD) alone and in combination. Combinations were more effective in inhibiting colony formation at lower concentrations than either drug alone.</p>

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

Selleck's AZD6244 (Selumetinib) Has Been Cited by 737 Publications

Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells [ Nat Commun, 2025, 16(1):4884] PubMed: 40419504
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
GCLM lactylation mediated by ACAT2 promotes ferroptosis resistance in KRASG12D-mutant cancer [ Cell Rep, 2025, 44(6):115774] PubMed: 40503938
Targeting LINC02320 prevents colorectal cancer growth via GRB7-dependent inhibition of MAPK signaling pathway [ Cell Mol Biol Lett, 2025, 30(1):86] PubMed: 40691533
Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C [ Cancer Gene Ther, 2025, 10.1038/s41417-025-00874-z] PubMed: 39915607
Fibroblasts Attenuate Anti-Tumor Drug Efficacy in Tumor Cells via Paracrine Interactions with Tumor Cells in 3D Plexiform Neurofibroma Cultures [ Cells, 2025, 14(16)1276] PubMed: 40862755
Basroparib overcomes acquired resistance to MEK inhibitors by inhibiting Wnt-mediated cancer stemness in KRAS-mutated colorectal cancer [ Biochem Pharmacol, 2025, 235:116842] PubMed: 40024348
Molecular Evidence Supporting MEK Inhibitor Therapy in NF1 Pseudarthrosis [ J Bone Joint Surg Am, 2025, 107(10):1098-1106] PubMed: 40168468
Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells [ Mol Cancer Res, 2025, 23(2):128-142] PubMed: 39485528
Secreted Cytokines From Inflammatory Macrophages Modulate Sex Differences in Valvular Interstitial Cells on Hydrogel Biomaterials [ J Biomed Mater Res A, 2025, 113(3):e37885] PubMed: 39995146

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