Pexmetinib (ARRY-614) is an orally bioavailable dual p38 MAPK/Tie-2 inhibitor studied in acute myeloid leukemia and inhibits osteoclastogenesis and breast cancer-induced osteolysis via the P38/STAT3 signaling pathway.

Tie2:18 nM, p38 MAPK:4 nM

METHODS: HEK-Tie2 cells were treated with Pexmetinib (ARRY-614) (0.05, 0.15, 0.5, 1.3, 4.1, 12, 37, 333, 1000 nM), and Western blot was used to evaluate the efficacy of direct or proximal inhibition of p-Tie-2 and p-p38 MAPK.
RESULTS The IC50 values ​​of Pexmetinib for inhibition of p-Tie-2 and p-p38 in cells were 16 and 1 nM, respectively. [1]
METHODS: MDA-MB-231 cells were treated with pexmetinib (ARRY-614) (4 μM), and the levels of the indicated proteins were measured by Western blotting at 0 h, 6 h, 12 h, and 24 h after treatment.
RESULTS Pexmetinib treatment inhibited the phosphorylation of p38 and STAT3 in MDA-MB-231 cells. [2]

METHODS: Pexmetinib (ARRY-614) Pexmetinib (10 mg/kg, intraperitoneal injection, once every 3 days, 1 month) was used to treat tumor xenograft model mice injected with MDA-MB-231 cells into the tibia to test the effect of Pexmetinib on breast cancer cells Caused by osteolytic bone damage.
RESULTS Tissue volume, tissue length, and tissue weight were reduced in xenograft mice treated with Pexmetinib; p-STAT3 was significantly reduced in the Pexmetinib-treated group. [2]