Binimetinib CAS NO.606143-89-9

Binimetinib Basic information
Kinase inhibitor Mechanism of Action Pharmacokinetics Binding Mode
Product Name:    Binimetinib
Synonyms:    5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide;MEK162 (ARRY-438162);MEK162 (ARRY-162, ARRY-438162);BiniMetinib (MEK162, ARRY-162, ARRY-438162);1H-Benzimidazole-6-carboxamide, 5-[(4-bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-;5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide Binimetinib (MEK162, ARRY-162, ARRY-438162);ARRY-438162 5-[(4-Bromo-2-fluorophenyl)amino]-4-fluoro-N-(2-hydroxyethoxy)-1-methyl-1H-benzimidazole-6-carboxamide;Binimetinib
CAS:    606143-89-9
MF:    C17H15BrF2N4O3
MW:    441.23
EINECS:    
Product Categories:    Inhibitors;API;MAPK
Mol File:    606143-89-9.mol

Binimetinib Chemical Properties
Melting point     >203oC (dec.)
density     1.67
storage temp.     -20°C
solubility     Soluble in DMSO (up to at least 25 mg/ml)
form     solid
pka    14.20±0.10(Predicted)
color     White
Stability:    Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

Binimetinib Usage And Synthesis
Kinase inhibitor    Binimetinib, also known as Mektovi, is a potent and selective oral mitogen-activated protein kinase 1/2 (MEK 1/2) inhibitor with potential antineoplastic activity.
Binimetinib, noncompetitive with ATP, binds to and inhibits the activity of MEK1/2. Inhibition of MEK1/2 prevents the activation of MEK1/2 dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling. This may eventually lead to an inhibition of tumor cell proliferation and an inhibition in production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor.
Mechanism of Action    Binimetinib is a reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. In vitro, binimetinib inhibited extracellular signal-related kinase (ERK) phosphorylation in cellfree assays as well as viability and MEK-dependent phosphorylation of BRAF-mutant human melanoma cell lines. Binimetinib also inhibited in vivo ERK phosphorylation and tumor growth in BRAF-mutant murine xenograft models.
Pharmacokinetics    The primary metabolic pathway is glucuronidation with UGT1A1 contributing up to 61% of the binimetinib metabolism. Other pathways of binimetinib metabolism include N-dealkylation, amide hydrolysis, and loss of ethane-diol from the side chain. The active metabolite M3 produced by CYP1A2 and CYP2C19 represents 8.6% of the binimetinib exposure. Following a single oral dose of 45 mg radiolabeled binimetinib, approximately 60% of the circulating radioactivity AUC in plasma was attributable to binimetinib.