Degradation of Cyclin K/CDK12 is a druggable vulnerability of colorectal cancer (H012)

Here, we screened a library of non-characterized small molecules against CRC patient-derived tumor spheroid culture (TSC) cells to identify a compound (NCT02) with activity in a subset of TSCs. Transcriptomics as well as thermal proteome profiling and chemical proteomics identified degradation of cyclin K (CCNK) and CDK12 as central mechanism-of-action, associated with increase of DNA damage and induction of apoptosis.EGA study EGAS00001004517