Product Categories

AZD6244 (Selumetinib)

AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM.

Catalog No.S1008
5 5 10 Reviews 44 Product Citations
Price Stock Quantity  
USD 90 In stock
USD 130 In stock
USD 170 In stock
USD 370 In stock
Contact Us Bulk Inquiry Add to Wishlist

Free Overnight Delivery on all orders over $ 500.

Order now and get it on

Tel: +1-832-582-8158[email protected]

AZD6244 (Selumetinib) Chemical Structure
Molecular Weight: 457.68

Validation & Quality Control

Product Citations(44)

Customer Reviews(10)

Quality Control & MSDS

Related Compound Libraries

AZD6244 (Selumetinib) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Products used with AZD6244 (Selumetinib) in previous publications

Targets Related Products References Purpose
MEK inhibitors U0126-EtOH [11][12][16] Positive Control. Compared to the MEK inhibition potency of AZD6244, CI-1040, U0126, PD98059, and PD0325901.
CI-1040 [16][15][6]
PD98059 [10][12][15]
PD0325901 [3][4]
PI3K inhibitors LY294002 [2][7][9] Mechanism of resistance to MEK inhibitors that can be overcome by PI3K inhibitors.Combination of P3K and MEK inhibitors for synergistically treating cancer: AZD6244 synergizes with PI3K inhibitors to suppress cancer cell proliferation and trigger apoptosis in a highly efficient manner.
NVP-BEZ235 [2][7][9]
mTOR inhibitors Rapamycin [7][9][13] Synergism is seen between the mTOR inhibitor and the MEK inhibitor.
Thyroid cancer clinical trials using combinations of MEK and mTOR inhibitors, targeting both pathways provides highly effective growth inhibition in cancer.
AZD8055 [9][13]
Raf inhibitors PLX4032 [5][11][16] The combination of Raf and MEK inhibition can not only overcome the resistance caused by Raf amplification but also potentially enhance antitumor efficacy and lower effective doses of each drug.
PLX4720 [4][11][6]
AZ628 [4][6]
SB590885 [11][6]
EGFR inhibitors Erlotinib [3][1][14] A major downstream target of the EGFR signaling cascade is ERK. MEK plays a central role in integrating mitogenic signals into the ERK pathway.
Gefitinib [12][8][14]
Lapatinib [8][6][14]

Product Information

  • Combination Therapy
    Combination Therapy
  • Compare MEK Inhibitors
    Compare MEK Inhibitors
  • Research Area

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description AZD6244 (Selumetinib, ARRY-142886) is highly potent to inhibit MEK1 with IC50 of 14 nM.
Targets

MEK1
IC50

14 nM [1]
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]
Clinical Trials AZD6244 is current in Phase II clinical trial against non-small-cell lung carcinoma (NSCLC).
Features AZD6244 is the first MEK inhibitor to be evaluated in randomised Phase II studies.

Protocol(Only for 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
Formulation In water
Dosages 50 or 100mg/kg
Administration Administered via p.o.
1

References

Chemical Information

Download AZD6244 (Selumetinib) SDF
Molecular Weight (MW) 457.68
Formula

C17H15BrClFN4O3
CAS No. 606143-52-6, 942275-12-9 (4-methylbenzenesulfonate)
Synonyms ARRY-142886
Solubility (25°C)
  • DMSO 92 mg/mL
  • Water <1 mg/mL
  • Ethanol <1 mg/mL
Storage 2 years -20°CPowder
2 weeks4°Cin DMSO
6 months-80°Cin DMSO
Chemical Name 6-(4-bromo-2-chlorophenylamino)-7-fluoro-N-(2-hydroxyethoxy)-3-methyl-3H-benzo[d]imidazole-5-carboxamide
Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

Customer Reviews (10)


Click to enlarge 		Rating
Source Oncogene, 2012, 31, 3277–3286. AZD6244 (Selumetinib) purchased from Selleck
Method Western Blot
Cell Lines HEK-293 cells
Concentrations 1 uM
Incubation Time
Results We cultured HEK-293 cellsstably overexpressing p37d or p110d with the general PI3K –inhibitor, LY294002, or the MAPK-inhibitor, AZD6244. The inhibitors strongly affected the levels ofphosphorylated AKT S473 and ERK.

Click to enlarge 		Rating
Source Nat Genet, 2011, 43(11), 1119-26.. AZD6244 (Selumetinib) purchased from Selleck
Method Immunoblot analysis/Flow cytometry analysis
Cell Lines melanoma cell lines
Concentrations 0-30 μM
Incubation Time 1 h/72 h
Results Exposure of melanoma cells to AZD-6244 inhibited MEK in mutant as well as in wild-type cells (Fig. a). exposure of most melanoma cells expressing mutant forms of GRM3 were 2–200-fold more sensitive to AZD-6244 compared to wild-type GRM3 cells (Fig. b). melanoma cell lines harboring mutant GRM3 are markedly more sensitive to MEK1/2 inhibition by AZD-6244, leading to increased cell death.

Click to enlarge 		Rating
Source Cancer Res, 2010, 70, 4709-4718. AZD6244 (Selumetinib) purchased from Selleck
Method Immunohistochemical staining and immunoblotting
Cell Lines HCT116 xenografts
Concentrations 25 mg/kg/bid
Incubation Time 21 d
Results AZD6244 significantly suppresses HCT116 colon cancer xenograft tumor growth in vivo.

Click to enlarge 		Rating
Source Br J Haematol, 2010, 149, 537–549. AZD6244 (Selumetinib) purchased from Selleck
Method [3H]thymidine uptake assay/TRAP assay
Cell Lines INA-6 MM cells, PBMCs
Concentrations 2-20000 nmol/l
Incubation Time 2/14 d
Results AS703026 inhibited growth of MM cells more potently than AZD6244 (Figs B). For example, the IC50 of AS703026 and AZD6244 against INA-6 cells was 10 and 100 nmol/l, respectively. AS703026 was also approximately 10-fold more potent than AZD6244 at inhibiting cytokine-induced osteoclast differentiation in vitro, as measured by number of TRAP-positive multinuclear cells following treatment of PBMCs with RANKL and M-CSF(Fig D).

Click to enlarge 		Rating
Source Dr Jong-In Park of Medical College of Wisconsin. AZD6244 (Selumetinib) purchased from Selleck
Method Western Blot
Cell Lines A375 cells
Concentrations 0-10 μM
Incubation Time 1/24 h
Results

Click to enlarge 		Rating
Source Cancer Res, 2010, 70, 4709-4718. AZD6244 (Selumetinib) purchased from Selleck
Method Immunoblotting
Cell Lines MDA-MB-435 cells, HCT116 cells, SW620 cells, HT29 cells, WM793 cells
Concentrations 10 μmol/L
Incubation Time 4 h
Results AZD6244 significantly inhibits ERK activation and increases FOXO3a expression in all these cancer cell lines, in which cell cycle arrest and apoptosis are concurrently enhanced.

Click to enlarge 		Rating
Source Nature, 2010, 468, 968-972. AZD6244 (Selumetinib) purchased from Selleck
Method Immunoblotting
Cell Lines A375 cells
Concentrations 1 μM
Incubation Time
Results Ectopic COT expression in A375 and SKMEL28 cells also conferred decreased sensitivity to the MEK inhibitors CI-1040 and AZD6244, suggesting that COT expression alone was sufficient to induce this phenotype. In the setting of ectopic COT expression, exposure to AZD6244 or CI-1040 in combination with PLX470 (1 μM each) reduced cell growth and pERK expression more effectively than did single-agent PLX4720, even at concentrations of 10 μM.

Click to enlarge 		Rating
Source PNAS, 2009, 106, 20411-20416. AZD6244 (Selumetinib) purchased from Selleck
Method Cell growth inhibition assays
Cell Lines melanoma cells
Concentrations 0.001-100 μM
Incubation Time 16 h
Results The GI50 for AZD6244 was 10-50 nM in treatment-naïve BRAFV600E melanoma cultures (WM3482, WM3457, and WM3506) but exceeded 2 μM in cells derived from the AZD6244-resistant metastasis (M307; Fig. A ). Likewise, marked biochemical inhibition of p-ERK was achieved follow ing a 16-hour exposure to 400 nM AZD6244 in treatment-naïve lines, but p-ERK remained robust in the resist ant cells even at 10 MAZD6244 (Fig. B ). Next, we introduced recombinant MEK1(P124L) into parental A375 cells and examined pharmacological resistance to MEK inhibition. As observed with the MEK1(P124S) allele above, MEK1(P124L) ex pression resulted in an ≈5-fold increase in AZD6244 GI50 when c ompared to A375, MEK-WT, or MEK-DD (Fig. C). Similarly, MEK1(P124L) conferred sustained p-ERK expression following exposure to varying concentrations of MEK inhibitor, with measureable p-ERK even at 2 μM of AZD6244 (Fig. D ). In contrast, parental A375 cells and those expressing

Click to enlarge 		Rating
Source Clin Cancer Res, 2010, 16, 6029-6039. AZD6244 (Selumetinib) purchased from Selleck
Method Clonogenic assays
Cell Lines melanoma cell lines
Concentrations 5000 nM
Incubation Time
Results Combinations were more effective in inhibiting colony formation at lower concentrations than either drug alone.

Click to enlarge 		Rating
Source NATURE, 2010, 468, 973-977. AZD6244 (Selumetinib) purchased from Selleck
Method Survival Assay
Cell Lines isogenic cell
Concentrations 0.01-10 μM
Incubation Time 72 h
Results The growth of M249 R4 and Pt55 R was sensitive to MEK inhibition in the presence of PLX4032

Product Citations (44)

  • Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. [Wilson TR, et al. Nature 2012;487(7408):505-9]

    PubMed: 22763448

  • Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. [Nazarian R, et al. Nature 2010;468(7326), 973-977]

    PubMed: 21107323

  • COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. [Johannessen CM, et al. Nature 2010;468(7326), 968-972]

    PubMed: 21107320

  • Exome sequencing identifies recurrent somatic MAP2K1 and MAP2K2 mutations in melanoma. [Nikolaev SI, et al. Nat Genet 2011;44(2):133-9]

    PubMed: 22197931

  • Exon capture analysis of G protein-coupled receptors identifies activating mutations in GRM3 in melanoma. [Prickett TD, et al. Nat Genet 2011;43(11):1119-26]

    PubMed: 21946352

  • MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling. [Huang S, et al. Cell 2012;151(5):937-50]

    PubMed: 23178117

  • Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma. [Smith MP, et al. J Natl Cancer Inst 2013;105(1), 33-46]

    PubMed: 23250956

  • Intestinal renin-angiotensin system is stimulated after deletion of Lkb1. [Shorning BY, et al. Gut 2012;61(2):202-13]

    PubMed: 21813469

  • MEK1 mutations confer resistance to MEK and B-RAF inhibition. [Emery CM, et al. Proc Natl Acad Sci U S A 2009;106(48), 20411-20416]

    PubMed: 19915144

  • Strong negative feedback from Erk to Raf confers robustness to MAPK signalling [Fritsche-Guenther R, et al. Mol Syst Biol 2011;7, 489]

    PubMed: 21613978

  • BH3-only protein silencing contributes to acquired resistance to PLX4720 in human melanoma. [Shao Y, et al. Cell Death Differ 2012;19(12):2029-39]

    PubMed: 22858545

  • Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EB-RAF inhibition. [Shi H, et al. Cancer Res 2011;71(15), 5067-5074]

    PubMed: 21803746

  • Activation of FOXO3a is sufficient to feverse mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor chemoresistance in human cancer. [Yang JY, et al. Cancer Res 2010;70(11), 4709-4718]

    PubMed: 20484037

  • Actin and ERK1/2-CEBPβ signaling mediates phagocytosis-induced innate immune response of osteoprogenitor cells. [Lee HG, et al. Biomaterials 2011;32(35), 9197-9206]

    PubMed: 21899882

  • MicroSCALE screening reveals genetic modifiers of therapeutic response in melanoma. [Wood KC, et al. Sci Signal 2012;5(224):rs4]

    PubMed: 22589389

  • Vertical targeting of the phosphatidylinositol-3 kinase pathway as a strategy for treating melanoma. [Aziz SA, et al. Clin Cancer Res 2010;16(24), 6029-6039]

    PubMed: 21169255

  • The Akt inhibitor MK2206 synergizes, but Perifosine antagonizes, the BRAFV600E inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. [Liu R, et al. J Clin Endocrinol Metab 2011;97(2), E173-182]

    PubMed: 22090271

  • p37δ is a new isoform of PI3K p111δ that increases cell proliferation and is overexpressed in tumors. [Fransson S, et al. Oncogene 2012;31(27):3277-86]

    PubMed: 22020336

  • p53 rescue through HDM2 antagonism suppresses melanoma growth and potentiates MEK inhibition. [Ji Z, et al. J Invest Dermatol 2011;132(2), 356-364]

    PubMed: 21993556

  • Treatment with selumetinib preserves cardiac function and improves survival in cardiomyopathy caused by mutation in the lamin A/C gene [Muchir A, et al. Cardiovasc Res 2012;93(2):311-9]

    PubMed: 22068161

  • Oncogenic MAP2K1 mutations in human epithelial tumors. [ Carcinogenesis 2012;33(5):956-61]

    PubMed: 22327936

  • Selective Cox-2 inhibitor celecoxib induces epithelial-mesenchymal transition in human lung cancer cells via activating MEK-ERK signaling. [Wang ZL, et al. Carcinogenesis 2013;34(3):638-46]

    PubMed: 23172668

  • Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. [Maira SM, et al. Mol Cancer Ther 2012;11(2), 317-328]

    PubMed: 22188813

  • A genome-scale RNA interference screen implicates NF1 loss in resistance to RAF inhibition. [Whittaker SR, et al. Cancer Discov 2013;ahead of print]

    PubMed: 23288408

  • Down-regulation of mitogen-inducible gene 6, a negative regulator of EGFR, enhances resistance to MEK inhibition in KRAS mutant cancer cells. [Yoon YK, et al. Cancer Lett 2012;316(1), 77-84]

    PubMed: 22082529

  • Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo. [Kim K, et al. Brit J Haematol 2010;149(4), 537-549]

    PubMed: 20331454

  • SHOC2 and CRAF Mediate ERK1/2 Reactivation in Mutant NRAS-mediated Resistance to RAF Inhibitor. [Kaplan FM, et al. J Biol Chem 2012;287(50):41797-807]

    PubMed: 23076151

  • Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. [Wang Y, et al. Mol Endocrinol 2011;25(12):2041-53]

    PubMed: 22053001

  • Glucose regulates cyclin D2 expression in quiescent and replicating pancreatic β-cells through glycolysis and calcium channels. [Salpeter SJ, et al. Endocrinology 2011;152(7):2589-98]

    PubMed: 21521747

  • Sorafenib and Mek inhibition is synergistic in medullary thyroid carcinoma in vitro. [Koh YW, et al. Endocr Relat Cancer 2012;19(1):29-38]

    PubMed: 22109971

  • FOXD3 regulates migration properties and Rnd3 expression in melanoma cells. [Katiyar P, et al. Mol Cancer Res 2011;9(5):545-52]

    PubMed: 21478267

  • An In Vivo C. elegans Model System for Screening EGFR-Inhibiting Anti-Cancer Drugs. [Bae YK, et al. PLoS One 2012;7(9):e42441]

    PubMed: 22957020

  • K-RAS mutant pancreatic tumors show higher sensitivity to MEK than to PI3K inhibition in vivo. [Hofmann I, et al. PLoS One 2012;7(8):e44146]

    PubMed: 22952903

  • Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway. [Atefi M, et al. PLoS One 2011;6(12):e28973]

    PubMed: 22194965

  • The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma. [Wu X, et al. PLoS One 2012;7(1):e29622]

    PubMed: 22253748

  • Involvement of epidermal growth factor receptor signaling in estrogen inhibition of oocyte maturation mediated through the G protein-coupled estrogen receptor (Gper) in zebrafish (Danio rerio). [Peyton C, et al. Biol Reprod 2011;85(1):42-50]

    PubMed: 21349822

  • Aggravation of Inflammatory Response by Co-Stimulation with Titanium Particles and Mechanical Perturbations in Osteoblast- and Macrophage- like Cells. [Lee HG, et al. Am J Physiol Cell Physiol 2012;ahead of print]

    PubMed: 23255578

  • Selective inhibition of extracellular signal-regulated kinases 1/2 blocks nerve growth factor to brain-derived neurotrophic factor signaling and suppresses the development of and reverses already established pain behavior in rats. [Matsuoka Y, et al. Neuroscience 2012;206, 224-236]

    PubMed: 22280975

  • Autophagic activation potentiates the antiproliferative effects of tyrosine kinase inhibitors in medullary thyroid cancer. [Lin CI, et al. Surgery 2012;152(6):1142-9]

    PubMed: 23158184

  • Preexisting MEK1 Exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors. [Shi H, et al. Cancer Discov 2012;2(5):414-24]

    PubMed: 22588879

  • Modeling of lamin A/C mutation premature cardiac aging using patient‐specific induced pluripotent stem cells. [Siu CW, et al. Aging 2012;4(11), 803-822]

    PubMed: 23362510

  • Inhibition of metadherin sensitizes breast cancer cells to AZD6244 [Kong X, et al. Cancer Biol Ther 2012;13(1):43-9]

    PubMed: 22336587

  • Simultaneous exposure of transformed cells to SRC family inhibitors and CHK1 inhibitors causes cell death. [Mitchell C, et al. Cancer Biol Ther 2011;12(3):215-28]

    PubMed: 21642769

  • Detection of Allosteric Kinase Inhibitors by Displacement of Active Site Probes. [Lebakken CS, et al. J Biomol Screen 2012;17(6):813-21]

    PubMed: 22453235

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions
Tel: +1-832-582-8158 Ext:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related MEK Inhibitors

  • CI-1040 (PD184352)

    CI-1040 (PD 184352) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM.

  • PD0325901

    PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM.

  • SL327

    SL327 is a selective inhibitor for MEK1 and MEK2 with IC50 of 0.18 μM and 0.22 μM, respectively.

  • U0126-EtOH

    U0126-EtOH is a highly selective inhibitor of MEK1 and MEK2 with IC50 of 0.07 μM and 0.06 μM, respectively.

  • PD98059

    PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM.

  • AS703026 (pimasertib)

    AS703026 is a highly selective and potent non-competitive inhibitor of MEK1/2 with IC50 of 5-11 nM.

  • BIX 02188

    BIX02188 is a selective inhibitor of MEK5 with IC50 of 4.3 nM.

  • BIX 02189

    BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM.

  • PD318088

    PD318088 is a non-ATP competitive allosteric MEK1/2 inhibitor.

  • AZD8330

    AZD8330 (ARRY-424704) is a MEK 1/2 inhibitor with IC50 of 7 nM.

MAPK Pathway Products

> Download

Recently Viewed Items

Tags: buy AZD6244 (Selumetinib) | AZD6244 (Selumetinib) supplier | purchase AZD6244 (Selumetinib) | AZD6244 (Selumetinib) cost | AZD6244 (Selumetinib) manufacturer | order AZD6244 (Selumetinib) | AZD6244 (Selumetinib) distributor
Contact Us