CyclinK degrader

CyclinK degrader refers to a class of targeted protein degraders (specifically molecular glues) that induce the degradation of Cyclin K (CCNK). In the context of IRICoR and RejuvenRx (a spin-off of ExCellThera), this program focuses on the development of proprietary small-molecule molecular glue degraders, such as UM511 and S656, for the treatment of oncology indications, particularly high-risk acute myeloid leukemia (AML). These compounds act by binding to the ATP-binding site of cyclin-dependent kinase 12 (CDK12) and promoting its interaction with the Cullin-RING E3 ubiquitin ligase 4 (CRL4) adaptor protein DDB1. This ternary complex formation brings Cyclin K into close proximity with the E3 ligase complex, leading to its polyubiquitination and subsequent proteasomal degradation. The depletion of Cyclin K disrupts the transcriptional elongation of DNA damage response (DDR) genes, leading to DNA lesions, cell cycle arrest, and apoptosis in cancer cells.

Other names

Cyclin K degrader