| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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Purity: ≥98%
| Targets |
MEK (IC50 = 12 nM); Autophagy
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| ln Vitro |
ARRY-438162 (625 nM) has an IC50 of 39 nM and prevents osteoclast differentiation in vitro. With an IC50 of 625 nM, ARRY-438162 (10 μM) inhibits in vitro osteoclast resorption. Weakly impairs osteoblast differentiation is ARRY-438162 (2 μM).[2]
ARRY-438162, a recently discovered potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of 11 nM.[3] MK-2206 (2 μM) and MEK162 (1 μM) together completely override the resistance of RSK-expressing MCF7 cells.[4] |
| ln Vivo |
ARRY-438162 (10 mg/kg, po, bid) reduces disease severity in rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models in a dose-dependent manner. In the rat collagen-induced arthritis (CIA) model, ARRY-438162 (po, bid) inhibits increases in ankle diameter by 27% and 50% at 1 mg/kg and 3 mg/kg, whereas ibuprofen has a 46% inhibition. In the rat collagen-induced arthritis (CIA) model, ARRY-438162 (10 mg/kg, po, bid) significantly inhibits lesions (inflammation, cartilage damage, pannus formation, and bone resorption) by 32% and 60% at 1 mg/kg and 3 mg/kg, respectively. In rat adjuvant-induced arthritis (AIA) models, ARRY-438162 inhibits AIA ankle diameter by 11% and 34% at 3 mg/kg and 10 mg/kg, respectively.[1]
ARRY-438162 is significant at 10 mg/kg and 30 mg/kg when compared to vehicle control, demonstrating dose-related inhibition of ankle swelling in rat adjuvant-induced arthritis (AIA) models. In rat adjuvant-induced arthritis (AIA) models, ARRY-438162 exhibits dose-related inhibition of serum IL-6 concentration, with complete inhibition at 10 mg/kg when compared to vehicle control. Rat adjuvant-induced arthritis (AIA) models show dose-related inhibition of relative spleen weights by ARRY-438162 (30 mg/kg). In rat adjuvant-induced arthritis (AIA) models, ARRY-438162 (30 mg/kg) significantly inhibits bone resorption and inflammation with delayed dosing when compared to vehicle.[2] In immunodeficient mice injected with MCF7 cells, MEK162 (6 mg/kg, BID) and BEZ235 significantly slow tumor growth. [4] |
| Enzyme Assay |
The in vitro osteoclast differentiation inhibitor ARRY-438162 (625 nM) has an IC50 value of 39 nM. The in vitro osteoclast resorption is inhibited by ARRY-438162 (10 μM) with an IC50 of 625 nM. Osteoblast differentiation is only marginally impacted by ARRY-438162 (2 μM). A recently discovered MEK1/2 ATP non-competitive inhibitor, ARRY-438162, inhibits pERK in cells with an IC50 of 11 nM. MCF7 cells that express RSK are completely resistant until MEK162 (1 μM) and MK-2206 (2 μM) are added.
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| Cell Assay |
In 12-well plates (2×104), MCF7 cells with the indicated infection level are seeded. Cells are exposed to BEZ235 (100 or 200 nM), BKM120 (0.75 or 1 μM), GDC-0941 (1 μM), or MK2206 (2 μM) alone or in combination with Binimetinib (MEK162) (1 μM), BI-D1870 (10 μM), or AZD6244 (1 μM), as indicated in the text, after 24 hours. Cells are stained with 0.1% crystal violet after being fixed with 4% glutaraldehyde or methanol, in order to determine how many cells are present. The dye is then extracted with 10% acetic acid, and its absorbance (570 nm) is measured. Growth curve analyses are carried out in triplicate. For CellTiter-Glo viability assays, 2,000 cells are plated in 96-well plates, the drug is added at 24 hours, and the assay is conducted 4 to 5 days later. Through the use of flow cytometry, cell-cycle and hypodiploid apoptotic cell numbers can be measured. In a nutshell, cells are PBS-washed, fixed in cold 70% ethanol, and stained with propidium iodide while being subjected to RNase. A FACScalibur cytometer equipped with Cell Quest software is used to quantitatively analyze sub-G1 cells.
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| Animal Protocol |
Mice: six-week-old athymic nude female The mice are Foxn1nu mice. Mice are given an oral gavage dose of the following drugs once daily: placebo, BEZ235, BKM120, MK-2206, or binimetinib (MEK162). BKM120 (30 mg/kg, 6IW) and BEZ235 (25-30 mg/kg, 6IW [6 days on, 1 day off]) are freshly formulated in 10% NMP-90% PEG and administered within 30 minutes. Binimetinib (MEK162) (6 mg/kg, BID) is formulated in 0.5% Tween-80 and 1% carboxymethyl cellulose with MK-2206 (100 mg/kg, 3IW) in 30% Captisol. Depending on the xenograft model and treatment regimen, mice are given treatment for 7–24 days in tumor growth studies. Three times per week, tumor xenografts are measured with calipers, and the tumor volume is calculated using the formula: (length×width2)×(π/6). The animals are anesthetized with a 1.5% isofluorane-air mixture before being killed by cervical dislocation at the conclusion of the experiment. Approximately two hours after the last administration, tumors are removed.
Rats: The effectiveness in the subacute inflammation setting is evaluated using the rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models. In the CIA studies, rats with established disease that was induced by Type II collagen injections were given 0.3, 1 or 3 mg/kg of ARRY-438162 (PO, BID) with or without 30 mg/kg of ibuprofen (PO, QD) for six days. Days 0–7 are used to track disease progression using body weight and ankle diameter. An injection of a lipoidal amine in FCA on day 0 induces the AIA model. The AIA rats are administered 1, 3, or 10 mg/kg of binimetinib (ARRY-438162) (PO, QD) starting on day 8 and continuing for 6 days, with or without the addition of 0.05 mg/kg of CL14377 (PO, QD), which is dosed days 0–13. On days 7 through 14, measurements of the paw diameter and body weight are used to track the disease's progression.
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| References |
| Molecular Formula |
C17H15BRF2N4O3
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|---|---|---|
| Molecular Weight |
441.23
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| Exact Mass |
440.03
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| Elemental Analysis |
C, 46.28; H, 3.43; Br, 18.11; F, 8.61; N, 12.70; O, 10.88
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| CAS # |
606143-89-9
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)F)C(=O)NOCCO
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| InChi Key |
ACWZRVQXLIRSDF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15BrF2N4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
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| Chemical Name |
6-(4-bromo-2-fluoroanilino)-7-fluoro-N-(2-hydroxyethoxy)-3-methylbenzimidazole-5-carboxamide
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| Synonyms |
MEK162; ARRY 162; ARRY-162; ARRY-438162; ARRY438162; MEK-162; MEK 162; ARRY162; ARRY-162; ARRY-438162; Binimetinib; Brand name: Mektovi.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2664 mL | 11.3320 mL | 22.6639 mL | |
| 5 mM | 0.4533 mL | 2.2664 mL | 4.5328 mL | |
| 10 mM | 0.2266 mL | 1.1332 mL | 2.2664 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04655157 | Active Recruiting |
Drug: encorafenib Drug: binimetinib |
Melanoma | Jason J. Luke, MD | April 2010 | Phase 1 Phase 2 |
| NCT03475004 | Active Recruiting |
Drug: Binimetinib Drug: Bevacizumab |
Colorectal Cancer Metastatic Cancer |
University of Colorado, Denver | September 17, 2018 | Phase 2 |
| NCT01909453 | Active Recruiting |
Drug: LGX818 Drug: MEK162 |
Melanoma | Pfizer | December 13, 2013 | Phase 3 |
| NCT05260684 | Active Recruiting |
Drug: Encorafenib Drug: Binimetinib |
Melanoma | Pfizer | January 17, 2022 | |
| NCT04439344 | Active Recruiting |
Drug: Binimetinib | Advanced Lymphoma Refractory Lymphoma |
National Cancer Institute (NCI) |
May 31, 2016 | Phase 2 |
Inhibition of ERK/RSK signaling overcomes resistance to PI3K inhibitors.J Clin Invest.2013 Jun;123(6):2551-63. |
Aberrant activation of MEK signaling confers the regained growth of Her2 positive mammary tumors.Oncogene.2016 Jun 9;35(23):2961-70. |
PI3K activation confers intrinsic resistance to Her2 inhibition by lapatinib.Oncogene.2016 Jun 9;35(23):2961-70. |
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