Pimasertib

Pimasertib (AS703026) is a highly selective, ATP non-competitive allosteric orally available MEK1/2 inhibitor^[1][2]. In Vitro: Pimasertib (5, 0.5, and 0.1 μM) specifically blocks ERK1/2 activation in MM cells, cultured alone or with BMSCs. Pimasertib inhibits the growth of MM cell lines in a dose-dependent manner, with IC₅₀s ranging from 0.005 to 2 μM. The IC₅₀s of Pimasertib against INA-6, U266, H929 cells are 10 nM, 5 nM, 200 nM respectively. Pimasertib induces apoptosis and modulates the cell cycle profile. Pimasertib targets MM cells in the BM microenvironment^[1]. Pimasertib (10 μmol/L) inhibits ERK pathway, proliferation, and transformation in cetuximab-resistant D-MUT cells^[2]. Pimasertib in combination with PLX4032 significantly induces apoptosis of RPMI-7951 cells, whereas each drug used alone does not. Pimasertib synergizes with small interfering RNA-mediated downregulation of BRAF to produce results similar to those of combined treatment with PLX4032 and Pimasertib^[3]. In Vivo: Pimasertib (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft model in CB17 SCID mice^[1]. Pimasertib (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumor attributed by K-ras mutation^[2].