Binimetinib (MEK162)

Catalog No.S7007 Batch:S700704

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Technical Data

Formula

C17H15BrF2N4O3
Molecular Weight 441.23 CAS No. 606143-89-9
Solubility (25°C)* In vitro DMSO 88 mg/mL (199.44 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 A potent inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay, Binimetinib (MEK162, ARRY-162, ARRY-438162) induces G1 cell cycle arrest and apoptosis in human NSCLC cell lines and also triggers autophagy. Phase 3.
Targets
MEK [1]
(Cell-free assay)
12 nM
In vitro

Binimetinib (MEK162) is a recently disclosed potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of11 nM. [3]

This compound (625 nM) inhibits in vitro osteoclast differentiation with IC50 of 39 nM. It (10 μM) inhibits in vitro osteoclast resorption with IC50 of 625 nM. It (2 μM) weakly affects osteoblast differentiation. [2]

MEK162 (1 μM) combined with MK-2206 (2 μM) completely reverses the resistance of RSK-expressing MCF7 cells. [4]
In vivo

Binimetinib (MEK162) reduces disease severity in a dose-related manner in rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models at 10 mg/kg (po, bid). In the rat CIA model, this compound (po, bid) inhibits increases in ankle diameter by 27% and 50% at 1 mg/kg and 3 mg/kg, while ibuprofen has 46% inhibition. It significantly inhibits lesions (inflammation, cartilage damage, pannus formation and bone resorption) by 32% and 60% at 1 mg/kg and 3 mg/kg in the same model. In rat AIA models, it inhibits ankle diameter 11% and 34% at 3 mg/kg and 10 mg/kg. [1]

It demonstrates dose-related inhibition of ankle swelling in rat AIA models, significant at 10 mg/kg and 30 mg/kg when compared to vehicle control. This compound also shows dose-related inhibition of serum IL-6 concentration in rat AIA models, with complete inhibition at 10 mg/kg when compared to vehicle control. At 30 mg/kg, it demonstrates dose-related inhibition of relative spleen weights in rat AIA models. Additionally, it significantly inhibits bone resorption and inflammation with delayed dosing when compared to vehicle in rat AIA models at 30 mg/kg. [2]

When combined with BEZ235 at 6 mg/kg (BID), it results in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells. [4]

Protocol (from reference)

Animal Study:

[4]
  • Animal Models

    immunodeficient mice injected with MCF7-RSK4 cells.

  • Dosages

    6 mg/kg

  • Administration

    oral

References

  • https://acr.confex.com/acr/2006/webprogram/Paper5558.html
  • http://www.arraybiopharma.com/_documents/Publication/PubAttachment349.pdf
  • http://www.sciencedirect.com/science/article/pii/S0065774307420176
  • https://pubmed.ncbi.nlm.nih.gov/23635776/
  • https://pubmed.ncbi.nlm.nih.gov/32442403/

Customer Product Validation

Whole-cell lysates from NRAS- or BRAF-mutant melanoma cells treated with encorafenib or/and binimetinib or DMSO as a control for 24 hours were subjected to Western blot analysis to detect pERK, ERK, andb-actin. The experiment shown is a representative of three independent experiments.

Data from [ , , Clin Cancer Res, 2017, 23(20):6203-6214 ]

A875 and WM2664 cells were transfected with Myc-NRAS plasmid (2.5 ug, 24 h) and NRAS siRNA (10 nM, 48 h), respectively, then were treated with indicated inhibitor for 48 h. The activation of indicated molecules and NRAS were examined by Western Blotting (A and D). The relative phosphorylation levels of signalling mediators were quantified by measuring the relative intensity of phosphorylated bands to the corresponding total bands (BeC and EeF; presented as mean±standard deviation [SD] of three scans)

Data from [ , , Eur J Cancer, 2018, 89:90-101 ]

Cells seeded in 96-well plates (2,000-3,000 cells per well) were cultured in triplicate with or without graded concentrations of MEK1/2 plus/minus 100 μg/mL cetuximab, which were not renewed during the entire period of cell exposure. For each pair of columns, the height of the left columns represents the sum of the toxic effect of each agent and, therefore, the expected toxicity if their effects were additive when used in combination. The total height of the right columns represents the observed toxicity when the agents were used in combination. The difference between the heights of the paired columns reflects the magnitude of antagonism or synergism on cell toxicity between MEK1/2 inhibitors and cetuximab in NRAS<sup>+/+</sup> (left panels) and NRAS<sup>Q61K/+</sup> (right panels) cells. Results are shown as mean (columns) ± SD (error bars) from at least three experiments in which triplicate wells were analyzed.

Data from [ , , Oncotarget, 2016, 7(50):82185-82199 ]

H460 cells were either treated with perifosine (3 μM), MEK-162 (1 μM), or combine for 8 h; expression of indicated proteins was tested by Western blots using corresponding antibodies.

Data from [ , , Tumor Biol, 2015, 36: 5699-06 ]

Selleck's Binimetinib (MEK162) Has Been Cited by 110 Publications

Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases [ Cell Rep Med, 2025, 6(2):101943] PubMed: 39922199
Geometric deep learning and multiple-instance learning for 3D cell-shape profiling [ Cell Syst, 2025, 16(3):101229] PubMed: 40112779
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
Integration of focal adhesion morphogenesis and polarity by DOCK5 promotes YAP/TAZ-driven drug resistance in TNBC [ Mol Omics, 2025, 10.1039/d4mo00154k] PubMed: 40353692
Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer [ Nature, 2024, 629(8013):927-936] PubMed: 38588697
MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB [ Signal Transduct Target Ther, 2024, 9(1):293] PubMed: 39438476
Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through one-carbon metabolism [ Nat Commun, 2024, 15(1):8178] PubMed: 39289374
EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway [ Acta Pharm Sin B, 2024, 14(3):1187-1203] PubMed: 38486999
Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] PubMed: 39319271

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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.

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