Senexin A

Senexin A is an inhibitor of CDK8/19 (IC₅₀: 280 nM, CDK8) and an inhibitor downstream of p21 transcription. It only inhibits p21-induced transcription but does not inhibit other biological effects of p21. Senexin A inhibits CMV-GFP induction as well as the p21 stimulatory activity of the consensus NF-κB-dependent promoters^[1][2]. IC50 & Target:IC50: 280 nM (CDK8)^[1]
Kd: 0.83 μM (CDK8), 0.31 μM (CDK19)^[1] In Vitro:Senexin A inhibits CDK8 and CDK19 ATP site binding with K_d50 of 0.83 μM and 0.31 μM, respectively^[1].
Senexin A inhibits β-catenin-dependent transcription in HCT116 colon cancer cells^[1].
In HT1080 cells, Senexin A strongly inhibits the induction of the transcription factor EGR1 upon serum starvation^[1].
Senexin A also reduces the expression of many secreted tumor-promoting factors in doxorubicin-treated wild-type HCT116 cells^[1].
In Vivo:Five daily treatment of Senexin A fully reverses tumor-promoting effect of chemotherapy. Senexin A shows no detectable toxicity and no significant effects on body weight, organ weights, or blood cell counts in C57BL/6 mice during the treatment. This effect of doxorubicin treatment is completely abolished, however, when doxorubicin injection is followed by administration of Senexin A. Senexin A treatment strongly improves the response of A549/MEF tumors to doxorubicin^[1].