product name Binimetinib
Description: Binimetinib, also known as MEK162, ARRY-162, ARRY-438162, is a potent and highly selective inhibitor of MEK1/2 with IC50 of 12 nM in a cell-free assay. MEK162 showed significant antitumor activities in cell lines and animal models. MEK162 is the first targeted therapy to show activity in patients with NRAS -mutated melanoma and might offer a new option for a cancer with few effective treatments.
References: Annual Reports in Medicinal Chemistry, 2007, 42, 265–278; J Clin Invest. 2013 Jun;123(6):2551-63.
441.23
Formula
C17H15BrF2N4O3
CAS No.
606143-89-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 88 mg/mL (199.4 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% CMC+0.5% Tween-80: 30 mg/mL
Synonyms
MEK162, ARRY-162, ARRY-438162
other peoduct :
| In Vitro |
In vitro activity: ARRY-438162 (625 nM) inhibits in vitro osteoclast differentiation with IC50 of 39 nM. ARRY-438162 (10 μM) inhibits in vitro osteoclast resorption with IC50 of 625 nM. ARRY-438162 (2 μM) weakly affects osteoblast differentiation. ARRY-438162 is a recently disclosed potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of11 nM. MEK162 (1 μM) combined with MK-2206 (2 μM) completely reverses the resistance of RSK-expressing MCF7 cells. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | ARRY-438162 (10 mg/kg, po, bid) reduces disease severity in a dose-related manner in rat collagen-induced arthritis (CIA) and rat adjuvant-induced arthritis (AIA) models. ARRY-438162 (po, bid) inhibits increases in ankle diameter by 27% and 50% at 1 mg/kg and 3 mg/kg in the rat collagen-induced arthritis (CIA) model, while ibuprofen has 46% inhibition. 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 in the rat collagen-induced arthritis (CIA) model. ARRY-438162 inhibits AIA ankle diameter 11% and 34% at 3 mg/kg and 10 mg/kg in rat adjuvant-induced arthritis (AIA) models. ARRY-438162 demonstrates dose-related inhibition of ankle swelling in rat adjuvant-induced arthritis (AIA) models, significant at 10 mg/kg and 30 mg/kg when compared to vehicle control. ARRY-438162 demonstrates dose-related inhibition of serum IL-6 concentration in rat adjuvant-induced arthritis (AIA) models, with complete inhibition at 10 mg/kg when compared to vehicle control. ARRY-438162 (30 mg/kg) demonstrates dose-related inhibition of relative spleen weights 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 in rat adjuvant-induced arthritis (AIA) models. MEK162 (6 mg/kg, BID) combined with BEZ235 results in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells |
| Animal model | Immunodeficient mice injected with MCF7-RSK4 cells. |
| Formulation & Dosage | Formulated in 0.5% Tween-80, 1% carboxymethyl cellulose; 6 mg/kg; oral gavage |
| References | Annual Reports in Medicinal Chemistry, 2007, 42, 265–278; J Clin Invest. 2013 Jun;123(6):2551-63. |
