MEK162的生物活性

MEK162(ARRY-438162; ARRY-162) is a potent inhibitor of MEK1/2 with IC50 of 12 nM.
IC50 value: 12 nM [1]
Target: MEK1/2
in vitro: 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. [2] ARRY-438162 is a recently disclosed potent and selective ATP non-competitive MEK1/2 inhibitor, inhibits pERK in cells with an IC50 of11 nM. [3] MEK162 (1 μM) combined with MK-2206 (2 μM) completely reverses the resistance of RSK-expressing MCF7 cells. [4]
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 [1]. MEK162 (6 mg/kg, BID) combined with BEZ235 results in a significant reduction of tumor growth in immunodeficient mice injected with MCF7 cells [4].

相關(guān)文獻(xiàn)

[1]. J Pheneger, et al. 2006, ACR Annual Scientific Meeting. Abst 794.

[2]. D Wright, et al. 2009, Arraybiopharma. Abstract FRI0063.

[3]. SS Bhagwat, et al. Annu Rep Med Chem, 2007, 42, 265–278.

[4]. Serra V, et al. RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest, 2013, 123(6), 2551-2563.