| Name | Binimetinib |
| Description | Binimetinib (ARRY-162) is a MEK1/2 inhibitor (IC50=12 nM) with selective and oral activity. Binimetinib has antitumor activity for the treatment of metastatic melanoma that cannot be resected or has a BRAF V600E or V600K mutation. |
| Cell Research | MEK162 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[2]. MCF7 cells infected as indicated are seeded in 12-well plates (2×104). After 24 hours, cells are treated with BEZ235 (100 or 200 nM), BKM120 (0.75 or 1 μM), GDC-0941 (1 μM), or MK2206 (2 μM) alone or in combination with MEK162 (1 μM), BI-D1870 (10 μM), or AZD6244 (1 μM), as indicated in text. Cell numbers are quantified by fixing cells with 4% glutaraldehyde or methanol, washing the cells twice in Water, and staining the cells with 0.1% crystal violet. The dye is subsequently extracted with 10% acetic acid, and its absorbance is determined (570 nm). Growth curves are performed in triplicate. Viability assays with CellTiter-Glo are performed by plating 2,000 cells in 96-well plates, adding the drug at 24 hours, and assaying 4 to 5 days after drug addition. Cell-cycle and hypodiploid apoptotic cells are quantified by flow cytometry. Briefly, cells are washed with PBS, fixed in cold 70% ethanol, and then stained with propidium iodide while being treated with RNase. Quantitative analysis of sub-G1 cells is carried out in a FACScalibur cytometer using Cell Quest software[2]. |
| In vitro | In models of collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) in rats, ARRY-438162 demonstrated significant anti-inflammatory effects. At doses of 1/3 mg/kg administered twice daily orally (p.o.), ARRY-438162 reduced ankle diameter swelling by 27%/50% in the CIA model, outperforming ibuprofen's 46% reduction. Higher doses of 3/10 mg/kg showed 11%/34% inhibition of ankle swelling in the AIA model. Moreover, in immunodeficient mice injected with MCF7-RSK4 cells, the combination of ARRY-438162 (6 mg/kg, twice daily) with BEZ235 significantly diminished tumor growth. In the AIA rat model, ARRY-438162 (10 mg/kg) completely suppressed serum IL-6 concentrations in a dose-dependent manner compared to controls. Similarly, in both CIA and AIA rat models, administration of ARRY-438162 (10 mg/kg, twice daily p.o.) dose-dependently ameliorated disease severity. The same dosing regimen significantly mitigated lesions (inflammation, cartilage damage, angiogenesis, and bone resorption) in the CIA model, with 1/3 mg/kg doses inhibiting these effects by 32% and 60%, respectively. Furthermore, in the AIA rat model, ARRY-438162 at 10/30 mg/kg doses significantly and dose-dependently reduced ankle swelling compared to control groups. |
| In vivo | ARRY-438162 is an ATP non-competitive inhibitor for MEK1/2, capable of inhibiting intracellular pERK with an IC50 of 11 nM. When used in combination, MEK162 (1 μM) and MK-2206 (2 μM) can fully reverse the resistance of MCF7 cells expressing RSK. ARRY-438162 at 2 μM exhibits minimal impact on osteoblast differentiation. At a concentration of 10 μM, ARRY-438162 inhibits osteoclast resorption in vitro with an IC50 of 625 nM. Additionally, ARRY-438162 at 625 nM suppresses osteoclast differentiation in vitro with an IC50 of 39 nM. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 50 mg/mL (113.32 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | Inhibitor | MEK-162 | Mitogen-activated protein kinase kinase | MEK 162 | ARRY 162 | ARRY162 | ARRY438162 | MAPKK | MAP2K | Binimetinib | ARRY 438162 | inhibit | Autophagy | MEK |
| Inhibitors Related | Stavudine | Xylitol | Myricetin | Sodium 4-phenylbutyrate | Hydroxychloroquine | Guanidine hydrochloride | Taurine | Curcumin | Oxyresveratrol | Paeonol | Naringin | Gefitinib |
| Related Compound Libraries | Pain-Related Compound Library | Bioactive Compound Library | EMA Approved Drug Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Inhibitor Library | FDA-Approved Drug Library | Bioactive Compounds Library Max | Anti-Cancer Drug Library | Anti-Cancer Active Compound Library |
United States
