SAR125844 is a potent and selective MET kinase inhibitor with a favorable preclinical toxicity profile,(IC50=4.2 nM).

MET RTK:4.2 nM

MKN-45、Hs 746T 及 SNU-5 细胞在含有完整培养基的poly d-lysine 96孔板中种植。随后，孔板在逐渐增加的SAR125844浓度下孵育了1小时，按标准程序生成细胞裂解物，并评估pMETY1230/1234/1235水平。使用软件和四参数logistic模型[1]计算了IC50值。

SAR125844抑制了AXL的自磷酸化和TPM–NTRK1过度表达的KM12细胞系的细胞增殖，其IC50值分别为110和1,400nM/升，分别表明在基于细胞的实验中对AXL和NTRK1具有30倍和500倍的选择性指数。SAR125844的选择性概况在单数字nM抗增殖活性的MET依赖型细胞系中得到进一步证实，并且在不依赖MET途径的细胞中完全没有影响。这与ARQ197在MET依赖型和MET独立型肿瘤细胞系上具有相等的抗增殖活性形成对比[1]。

The antitumor activity of SAR125844 was investigated after administration of SAR125844 solution daily in SNU-5 bearing mice at 10, 20, and 45 mg/kg and every 2 days in Hs 746T tumor–bearing mice (at 5, 10, 20, and 45 mg/kg for SAR125844 solution and at 5, 11, 21, 53, 106, and 213 mg/kg for SAR125844 nanosuspension). Tumor volumes (in mm^3, based on the following formula, volume = length (mm) × width2 (mm2)/2), were measured twice weekly and body weight recorded every day. Endpoints collected were complete regressions (CR, regression below the palpable limit), partial regressions (PR, regression of 50% of the initial tumor volume), and the percentage of tumor regression (% of volume decrease posttreatment compared with pretreatment). Statistical significance was determined by a Dunnett test versus vehicle after a two-way ANOVA with repeated measures performed separately on ranks of changes from baseline with P < 0.05 considered significant[1].