SRI 31215 TFA, a small molecule that acts as a triplex inhibitor of matriptase, hepsin and HGFA and mimics the activity of HAI-1/2, endogenous inhibitors of HGF activation with IC50s of 0.69 μM, 0.65 μM, 0.3 μM,

Hepsin:0.65 μM , HGFA:0.3 μM, Matriptase:0.69 μM

SRI 31215 抑制成纤维细胞促进的MET激活、上皮-间充质转换以及癌细胞的迁移。它能克服HGF产生的结肠癌细胞对西妥昔单抗和吉非替尼的初级抗性，并阻止成纤维细胞介导的对表皮生长因子受体抑制剂的抗性。因此，SRI 31215 阻断癌细胞与成纤维细胞之间的信号传递，并抑制癌相关成纤维细胞的肿瘤促进活动。

DU145 cells were cultured in 6-well tissue culture plates at a density of 1 103 cells per well.?After colonies formed (6-8 days), cells were serum-starved overnight and were then treated with recombinant HGF (10 ng/ml) or with conditioned media from 18Co fibroblasts in the presence or absence of SRI 31215 (10 μM) or the MET kinase inhibitor JNJ 38877605 (1 μM) for 24 hours.?Cells were washed with PBS and colonies were fixed and stained with 0.5% crystal violet solution in 6% glutaraldehyde.