senexin a

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.

Senexin A hydrochloride functions as a selective inhibitor of CDK8/19, with an IC 50 of 280 nM for CDK8, and specifically inhibits p21-induced transcription without affecting other biological effects of p21. Additionally, it suppresses CMV-GFP induction and the stimulatory activity of the consensus NF-κB-dependent promoters [1] [2].

Senexin C is a novel orally active and specific CDK8/19 inhibitor with potential anticancer activity.Senexin C is more metabolically stable and potent than Senexin B. Senexin C inhibits the growth of MV4-11 leukaemia cells.

Senexin B is a potent and selective inhibitor of CDK8/19(CDK8 and CDK19 with Kds of 140 nM and 80 nM).

SNX631 is a potent and highly selective CDK8/19 mediator kinase inhibitor with an IC₅₀ of 10.3 nM in NF-κB-dependent cellular assays. Its activity is 6–10 times higher than that of Senexin B in all assays except DiscoverX active site-dependent competitive binding experiments. SNX631 exerts synergistic effects with lapatinib and trastuzumab in multiple HER2-positive breast cancer cell lines, reversing and preventing resistance to HER2-targeted therapy. The combination of trastuzumab (a HER2 monoclonal antibody) and SNX631 inhibits the phosphorylation of STAT1 and STAT3 at the S727 site and upregulates the expression of the tumor suppressor BTG2 in HER2-positive breast cancer cells. SNX631 partially inhibits the growth of lapatinib-sensitive and -resistant HER2-positive breast cancer xenografts, and its antitumor effect is significantly enhanced when combined with lapatinib, effectively overcoming lapatinib resistance.