Senexin A is an effective and selective CDK8 inhibitor that also inhibits CDK19 with Kd values of 0.83 microns and 0.31 microns, respectively.

CDK19:0.31 μm, CDK8:0.83 μM

Senexin A通过抑制CDK8和CDK19的ATP结合位点，其Kd50分别为0.83 μM和0.31 μM。Senexin A抑制CDK8的激酶活性，IC50为0.28 μM。CDK8可激活Wnt/β-catenin信号通路，而Senexin A能够抑制HCT116结肠癌细胞中依赖β-catenin的转录活动。

Senexin A能完全逆转化疗的肿瘤促进效应。Senexin A在治疗期间对C57BL/6小鼠没有检测到毒性，并且对体重、器官重量或血细胞计数没有显著影响。但是，当doxorubicin注射后紧接着使用Senexin A时，doxorubicin的效应完全被抵消。Senexin A治疗显著提高了A549/MEF肿瘤对doxorubicin的响应。

Tumor-free C57BL/6-derived SCID mice were injected with a single dose of doxorubicin or carrier control.?Five days later, mice received. injection of 2 × 10^6 human A549 lung carcinoma cells, and tumor take was measured over 4 wk.