YJ9069 is a selective CDK12/CDK13 PROTAC degrader with an IC 50 of 22.22 nM for in VCaP cells. CDK12/13 degradation rapidly triggers gene-length-dependent transcriptional elongation defects, leading to DNA damage and cell-cycle arrest. YJ9069 effectively inhibits proliferation in subsets of prostate cancer cells and significantly suppresses prostate tumor growth. (Pink: CDK12/CDK13 degradation agent ; Black: Linker ; Blue: ligand for E3 ligase ).