Senexin A

Senexin A is an inhibitor of cyclin-dependent kinase 8 (Cdk8; IC₅₀ = 0.28 µM).¹ It also inhibits cyclin-dependent kinase inhibitor p21^WAF1-induced reporter expression in reporter assay using HT-1080 p21-9 cells (IC₅₀ = 0.68 µM). Senexin A (2.5 µM) prevents 17β-estradiol-induced increases in expression of mRNA encoding gene regulated in breast cancer 1 (GREB1), chemokine (C-X-C motif) ligand 12 (CXCL12), and trefoil factor 1 (TFF1) in estrogen-deprived MCF-7, BT474, and T47D breast cancer cells.² It decreases intracellular and extracellular viral RNA, the number of infectious particles, as well as dengue virus-induced increases in the levels of mRNA encoding LC3-II in dengue virus-infected Huh7 cells when used at a concentration of 25 µM.³ Senexin A (12.5 µM) reduces mitochondrial oxygen consumption rate (OCR) and increases glycolysis in uninfected and dengue virus-infected Huh7 cells.

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1. Porter, D.C., Farmaki, E., Altilia, S., et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc. Natl. Acad. Sci. USA 109(34), 13799-13804 (2012).

2. McDermott, M.S., Chumanevich, A.A., Lim, C.-U., et al. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget 8(8), 12558-12575 (2017).

3. Butler, M., Chotiwan, N., Brewster, C.D., et al. Cyclin-dependent kinases 8 and 19 regulate host cell metabolism during dengue virus serotype 2 infection. Viruses 12(6), 654 (2020).