A Potent and Selective Small-Molecule STAT5 PROTAC Degrader Capable of Achieving Tumor Regression In Vivo

We have developed AK2292 as a first, potent and selective small-molecule degrader of both STAT5A and STAT5B isoforms. To investigate the effect of STAT5A/STAT5B depletion on the transcriptome, we treated KU812 and NCO2 cells with AK2292 at 1 μM for 8 h and performed RNA-seq analysis. As a control, we treated KU812 and NCO2 cells with AK2292Me at 5 μM for 24 h for RNA-seq analysis. RNA-seq analysis revealed that AK2292 downregulates the transcriptome associated with STAT5A and STAT5B. Comparative gene expression profiling analysis of RNA-seq data for KU812 and NCO2 cells treated with AK2292 and AK2292Me