SPI-21 (Spt5-Pol II inhibitor 21) is a small-molecule inhibitor of Spt5-Pol II with IC50 of 25.2 uM.
Short-term SPI-21 treatment to HeLa cells caused a transcription upregulation (≥2-fold) of 1,371 genes, among them A20 (TNFAIP3), IL-6, IL-8 (CXCL8), and CCL20 (analyzed above), while CXCL2, IEX1 (IER3), and JUNB were unchanged.
SPI-21 precisely mimics the effect of Spt5 depletion on basal and activated NF-κB target genes and on the expanded repeat Htt gene.
Spt5 is a conserved and essential transcription elongation factor that promotes promoter-proximal pausing, promoter escape, elongation, and mRNA processing.
SPI-21 is a useful chemical probe to elucidate the function of Spt5.
