Pimasertib (AS703026) is an orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity.

MEK1/2 (MM cell lines):5 nM-2 μM

10 mg/kg AS703026抑制人类K-Ras突变 (D-MUT) 的结肠直肠移植瘤生长,且明显降低p-ERK水平.15和30 mg/kg AS703026明显抑制人类浆细胞H929 mM移植瘤生长,这可能与下调的pERK1/2,诱导的PARP切割和微血管减少相关.

AS703026（10 μM）能有效抑制携带K-Ras突变等位基因（D-MUT）的人DLD-1结直肠癌细胞中的ERK途径,增殖和转化。AS703026抑制人类多发性骨髓瘤细胞(包括U266和INA-6细胞)生长和存活,IC50分别为5和11 nM。AS703026的这种抑制作用由G0-G1细胞周期停滞介导,并伴随MAF致癌基因表达减少。在存在或不存在骨髓基质细胞（BMSC）的情况下,AS703026通过半胱天冬酶-3和PARP在MM细胞中裂解进一步诱导细胞凋亡。 AS703026可有效治疗由K-Ras突变引起的结直肠癌。

The Aurora kinase activity is measured with 10 μM ATP and a peptide containing a dual repeat of the kemptide phosphorylation motif.

Method: Measuring incorporation of 14C-labelled thymidine into newly synthesized DNA within the cells to determine the ability of JNJ-7706621 to inhibit the proliferation of cell growth. Cells are trypsinized and counted and 3-8 ×103 cells are added to each well of a 96-well CytoStar tissue culture treated scintillating microplate in 100 μL complete medium in a volume. Cells are incubated for 24 hours at 37 °C in an atmosphere containing 5% CO2. Next, 1 μL JNJ-7706621 is added to the wells of the plate. Cells are incubated for another 24 hours. Methyl 14C-thymidine 56 mCi/mmol is diluted in complete medium and 0.2 μCi/well is added to each well of the CytoStar plate in a volume of 20 μL. The plate is incubated for 24 hours at 37 °C in JNJ-7706621 with 14C-thymidine. The contents of the plate are discarded and the plate is washed twice with 200 μL PBS. 200 μL of PBS is added to each well. The top of the plate is sealed with a transparent plate sealer and a white plate backing sealer is applied to the bottom of the plate. The degree of methyl 14C-thymidine incorporation is quantified on a Packard Top Count.