AS703026

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AS703026 (Pimasertib;MSC1936369B) 是一种有效的、选择性的、变构的、口服生物可利用的 MEK1/2 抑制剂。

AS703026 (Pimasertib;MSC1936369B) is a potent, selective, allosteric, orally bioavailable MEK1/2 inhibitor, inhibits the growth of MM cell lines with IC50 of 0.005-2 uM; has IC50 of 10 nM against INA-6 cells, approximately 10-fold more potent than AZD6244 at inhibiting cytokine-induced osteoclast differentiation in vitro; effectively inhibits the growth of D-MUT cells in vitro and in vivo by specific inhibition of the key MEK downstream target kinase ERK; also enhances gemcitabine efficacy in pancreatic cancer models by reducing ribonucleotide reductase subunit-1 (RRM1).Skin Cancer Phase 2 Clinical(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. Pimasertib (10 μmol/L) inhibits ERK pathway, proliferation, and transformation in cetuximab-resistant D-MUT cells. 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.(In Vivo):Pimasertib (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft model in CB17 SCID mice. Pimasertib (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumor attributed by K-ras mutation.

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. Pimasertib (10 μmol/L) inhibits ERK pathway, proliferation, and transformation in cetuximab-resistant D-MUT cells. 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.

Pimasertib (15, 30 mg/kg) significantly inhibits the growth of tumor in the human H929 MM xenograft model in CB17 SCID mice. Pimasertib (10 mg/kg, p.o.) inhibits tumor growth of cetuximab-resistant tumor attributed by K-ras mutation.

Pimasertib | MSC1936369B | AS-703026 | AS 703026

MAPK/ERK Signaling

MEK

MEK1/2(MMcellline)

Cancer

Skin Cancer

1236699-92-5

431.2008

C15H15FIN3O3

>98% (HPLC)

10 mM in DMSO

O=C(NC[C@H](O)CO)C1=CC=NC=C1NC2=CC=C(I)C=C2F

4-Pyridinecarboxamide, N-[(2S)-2,3-dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-

(-20℃)

With Ice Pack

≥ 2 years