cyclin k degrader

HQ461 is a molecular glue that promotes CDK12-DDB1 interaction, triggering cyclin K degradation, decreased CDK12 substrate phosphorylation, downregulation of DNA damage response genes, and cell death.

dCeMM3 (2-(1H-benzimidazol-2-ylsulfanyl)-N-(5-chloropyridin-2-yl)acetamide) is a glue degrader. dCeMM3 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, result in inducing ubiquitination and degradation of cyclin K.

dCeMM4 (Compound 5) is a glue degrader that promotes cyclin K ubiquitination and degradation by facilitating the interaction between CDK12-cyclin K and a CRL4B ligase complex [1].

dCeMM2 is a glue degrader. dCeMM2 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, leading to the ubiquitination and degradation of cyclin K.

PP-C8, a potent and selective PROTAC CDK12-Cyclin K degrader, efficiently induces degradation of CDK12 and Cyclin K, with DC50 values of 416 nM and 412 nM, respectively. This compound exhibits significant synergistic antiproliferative effects when combined with a PARP inhibitor in triple-negative breast cancer (TNBC) [1].